Automatic response/light measurement device and method therefor

ABSTRACT

The invention relates to an automatic response/light measurement device and a method therefor, and the purpose is to effectively and quickly perform an optical measurement relating to a reaction with high reliability without increasing a device size. The device is configured to have: a container group in which a plurality of reaction containers are arranged; a measurement mount provided with a plurality of coupling ends that are joinable with apertures of the reaction containers, and have light guide portions that optically connect with the interior of the joined reaction containers; a mount transfer mechanism; a measuring device provided on the mount and having a measuring end having at least one light guide portion that is optically connectable to the light guide portions of the coupling ends, that is able to receive light based on an optical state within the reaction containers via the measuring end; an on-mount measuring end transfer mechanism that makes the measuring end movable on the mount; and a measurement control portion that, following control of the mount transfer mechanism such that the coupling ends are simultaneously joined with the apertures of the reaction containers, controls the on-mount measuring end transfer mechanism such that the light guide portions of the coupling ends and the light guide portion of the measuring end are successively optically connected, and instructs a measurement by the measuring device.

CROSS REFERENCE

This application is a United States national phase application ofco-pending international patent application number PCT/JP2012/052632,filed Feb. 6, 2012, which claims priority to Japanese patent applicationnumber 2011-023378, filed Feb. 4, 2011, the disclosures of which areincorporated herein by reference.

TECHNICAL FIELD

The present invention relates to an automatic response/light measurementdevice and a method therefor.

BACKGROUND ART

At the time reactions such as amplification of nucleic acids (DNA, RNA,and the like) and the fragments thereof (oligonucleotides, nucleotides,and the like) are performed, in tests that require quantitativeness,such as the analysis of gene expression levels, it becomes necessary toperform the amplification such that the ratio of the relative amounts ofthe respective nucleic acids can be known. Consequently, by using thereal-time PCR method, and by using a device provided with a thermalcycler and a fluorescence spectrophotometer, analysis by electrophoresisis made unnecessary as a result of the generation process of the DNAamplification products in PCR being detected and analyzed in real time.Furthermore, as a DNA amplification method that performs amplificationwhile maintaining the quantitativeness with respect to the ratio of therelative amounts of the DNA or RNA contained in the sample beforeamplification, the SPIA (Single Primer Isothermal Amplification) methodis used. In the SPIA method, the linear DNA amplification methodresulting from an isothermal reaction utilizing DNA/RNA chimera primer,DNA polymerase, and RNaseH has become used.

In a case where processing such as nucleic acid amplification, andmeasurements thereof are performed, conventionally, the target compoundis separated and extracted from the sample by using a filter by means ofa manual method, by using magnetic particles and adsorption on an innerwall of a container or a pipette tip by means of a magnetic field, or byusing a centrifuge. The separated and extracted target compound istransferred and introduced into a reaction container together with areaction solution by a manual method and the like, and upon sealing ofthe reaction container using a manual method and the like, at the timereactions are performed using a temperature control device forreactions, optical measurements are performed with respect to thereaction container using a light measuring device (Patent Document 1).

In a case where the processing is executed by a manual method, a largeburden is forced on the user. Furthermore, in a case where theprocessing is executed by combining a dispenser, a centrifuge, amagnetic force device, a temperature controller, a device for sealingthe reaction container, a light measurement device, and the like, thereis a concern of the scale of the utilized devices increasing and of thework area expanding. In particular, in a case where a plurality ofsamples is handled, since it becomes necessary to separate and extract aplurality of target nucleic acids and for amplification to be torespectively performed, the labor thereof becomes even greater, andfurthermore, there is a concern of the work area also expanding further.

Specifically, in a case where reactions of the nucleic acids (DNA, RNA,and the like) to be amplified, and the like, are performed within aplurality of reaction containers and these reactions are monitored byoptical measurements, the measurements are performed by successivelymoving a single measuring device to the respective reaction containersby a manual method, or the measurements are performed by providing ameasuring device to each of the respective reaction containersbeforehand.

In the former case where a single measuring device is used, when themeasuring device is attempted to be manually moved to the apertures ofthe reaction containers, there is a concern of subtle differencesoccurring in the measurement conditions for each reaction container as aresult of subtle displacements or relative motions between the reactioncontainer and the measuring device.

In the latter case where a measuring device is provided to each of therespective reaction containers, although the positioning accuracybecomes high, there is a concern of the device scale expanding, and ofthe manufacturing costs increasing. Furthermore, although it ispreferable to seal the apertures of the reaction containers at the timeof temperature control and the measurements, it is time-consuming toperform sealing, or opening and closing, with respect to a plurality ofreaction containers by a manual method with a lid, and in particular,there is a concern of the lid becoming adhered to the containerapertures such that it becomes difficult to easily open the lid, and ofcontamination occurring from the liquid attached to the inside of thelid dripping or splashing. Furthermore, there is a concern of providinga dedicated opening and closing mechanism of the lid complicating thedevice, and increasing the manufacturing costs (Patent Document 2).

Moreover, at the time an optical measurement is performed on a sealedreaction container, there is a concern of the lid which hastransparency, or the optical elements, becoming cloudy fromcondensation, and the measurements becoming difficult.

Consequently, in order to perform nucleic acid amplification and thelike, as a precondition thereof, specialized researchers or techniciansbecome necessary, and this situation is preventing the generalization ofgenetic analysis and the expansion of clinical applications inhospitals, and the like.

Therefore, at the time of clinical use and the like, in order to preventcross-contamination and to reduce user labor, and to easily perform fromthe extraction, the amplification, and further, by means of ameasurement, the genetic analysis of nucleic acids, then the automationof steps from the extraction of the target compound, reactions such asamplification, up to the measurements, the miniaturization of thedevice, and the provision of an inexpensive, high-accuracy device areimportant.

PRIOR ART DOCUMENTS

[Patent Document 1] International Publication WO96/29602

[Patent Document 2] Japanese Unexamined Patent Publication No.2002-10777

SUMMARY OF THE INVENTION Problems to be Solved by the Invention

Therefore, the present invention is one that has been achieved in orderto solve the problems mentioned above. A first object thereof is inproviding an automatic response/light measurement device and anautomatic response/light measurement method that automates opticalmeasurements with respect to reactions of nucleic acids and the like,reduces user labor, performs processing rapidly and efficiently, andwhich also can be inexpensively manufactured and utilized withoutexpanding the scale of the device or complicating the device.

A second object thereof is in providing an automatic response/lightmeasurement device and an automatic response/light measurement method inwhich optical measurements with a high accuracy with respect to thesolutions within the reaction containers, in which reactions such asamplification of nucleic acids are performed, are possible.

A third object thereof is in providing an automatic response/lightmeasurement device and an automatic response/light measurement methodthat, by consistently automating the optical measurements with respectto the reaction containers, in which reactions such as amplification ofnucleic acids are performed, and the associated processing therein,processing with a high reliability can be performed by preventing withcertainty contaminations due to the entry of contaminants into thereaction containers from the exterior, or fluid leakage from thereaction containers for example.

Means for Solving the Problem

A first aspect of the invention is an automatic response/lightmeasurement device comprising: a container group in which two or morereaction containers are arranged; a measurement mount provided with twoor more coupling ends that are directly or indirectly joinable withapertures of the reaction containers, and have light guide portions thatoptically connect with the interior of the joined reaction containers; amount transfer mechanism that makes the mount relatively movable withrespect to the container group; a measuring device provided on the mountand having a measuring end having at least one light guide portion thatis optically connectable to the light guide portions of the couplingends, that is able to receive light based on an optical state within thereaction containers via the measuring end; an on-mount measuring endtransfer mechanism that makes the measuring end movable on the mount;and a measurement control portion that, following control of the mounttransfer mechanism such that the coupling ends are simultaneouslydirectly or indirectly joined with the apertures of the two or morereaction containers, controls the on-mount measuring end transfermechanism such that the light guide portions of the coupling ends andthe light guide portion of the measuring end are successively opticallyconnected, and instructs a measurement by the measuring device.

It is preferable for the container group to have in addition to thereaction containers, two or more liquid housing parts that house liquidssuch as samples, reagents, and the like. Furthermore, the containergroup includes a microplate in which wells representing a plurality ofliquid housing parts are arranged in a matrix form or a column (row)form, or a cartridge form container in which wells representing aplurality of liquid housing parts are arranged in a row form. In a casewhere amplification of nucleic acids is performed, the container groupis provided with two or more liquid housing parts housing for example; asample, a magnetic particle suspension in which magnetic particles thatare able to capture the nucleic acids or the fragments thereof, whichrepresent the amplification subject, are suspended, a solution forseparating and extracting used for the separation and the extraction ofthe amplification subject, and an amplification solution used in nucleicacid amplification.

Here, the “amplification solution” represents, in a case whereamplification is performed by the PCR method for example, a template DNAsolution which is the amplification subject, a primer solution, a DNApolymerase solution, a nucleotide solution, a reaction buffer solution,and the like. In a case where amplification is performed by the SPIAmethod, it represents a DNA/RNA chimera primer solution, a DNApolymerase solution, an RNaseH solution, and the like. Furthermore,generally, methods for performing real-time PCR using fluorescentreagents containing a fluorescent compound include the intercalationmethod, the hybridization method, and the LUX method. In the“intercalation method”, a fluorescent compound such as SYBR (registeredtrademark) GREEN I or ethidium bromide, enters into double-stranded DNAat the time of the elongation reaction, and is a method in which the DNAamount is measured by irradiating an excitation light and utilizing thefluorescent light-emitting characteristics. Therefore, at the veryleast, the fluorescent material and a quencher that suppresses the lightemission of the fluorescent material must be contained within theamplification solution. The “hybridization method” is a method thatdetects only a target PCR product by using a DNA probe labeled with afluorescent material in addition to a PCR primer. That is to say, as aresult of the DNA probe labeled by fluorescent material hybridizing withthe target PCR product, the hybridized DNA (amount) thereof is detected.The “LUX method” is one that utilizes a property in which thefluorescent light signal of the fluorescent compound labeling theoligonucleotide is affected by the shape (such as a sequence, asingle-strand, or a double-strand) of the oligonucleotide thereof. Inactual real-time PCR, a PCR primer (LUX primer) that is labeled with onetype of a fluorescent compound and a contrastingly unlabeled PCR primerare used to perform real-time PCR. The LUX primer thereof is labeledwith a fluorescent compound in the vicinity of the 3′-terminus, and isdesigned such that it takes a hairpin structure in the interval betweenthe 5′-terminus. When the LUX primer takes a hairpin structure, thequenching effect is resolved, and the fluorescent light signal becomesincreased. By measuring this signal increase, the amount of the PCRproduct can be measured.

Examples of the material of the containers, which includes the reactioncontainers, the lid, and the like, include resins such as polyethylene,polypropylene, polystyrene and acrylic, glass, metals, and metalcompounds. The size of the containers is, in addition to several μL toseveral 100 μL of liquid being storable, a size in which the ends of thedispensing tips are insertable for example. In the case of a cylindricalshape, the diameter of the size of one container is several mm toseveral 10 mm, and the depth is several mm to several 10 mm for example.

It is preferable for the interior of the reaction containers to betemperature controllable by a temperature controller.

The “temperature controller” has a temperature source that is able tolower the temperature within the reaction containers, which house theliquids that become subjected to temperature control, based on a signalfrom the exterior for example. The temperature source is one in which,for example, a Peltier element, a heater, a cooling device, and the likeis provided on a block-shaped member. In order to perform processingsuch as PCR, the temperature controller is preferably a thermal cyclerusing a Peltier element. It is preferable for temperature control to beachieved by a temperature controller provided to the container group orthe stage, in which a temperature source, which has a Peltier elementand the like, makes contact with or is adjacent to a portion or theentirety of the reaction container.

“Temperature control” represents, with respect to a liquid or acontainer that becomes the subject thereof, the maintaining of one ortwo or more set predetermined temperatures for set time periods,according to a specified sequence, and the execution at a specifiedfrequency. The instructions to the temperature controller are carriedout by sending a corresponding signal based on a program. An example oftemperature control includes temperature control by the LAMP methodusing isothermal amplification, which is also possible.

The “predetermined temperature” is a target temperature that an object,such as a liquid that becomes the subject, is to reach. In a case wherenucleic acids, such as the DNA contained in a liquid, oroligonucleotides and the like, which represent fragments of nucleicacids, are amplified by the PCR method for example, the predeterminedtemperature that is set is a temperature cycle performed in the PCRmethod. That is to say, it represents temperatures that are respectivelynecessary for the denaturation, the annealing or the hybridization, andthe elongation of DNA of approximately 94° C., a temperature in theinterval from 50° C. to 60° C., and a temperature of approximately 72°C. for example. On the other hand, in the case of the isothermal SPIAmethod, it becomes set at a fixed temperature, such as 55° C. forexample.

Furthermore, the predetermined temperature includes a temperature fortransition acceleration that shortens the transition time and keeps thesingle cycle time within a predetermined cycle time as a result of, inthe case of a transition from a high-temperature predeterminedtemperature to a low-temperature predetermined temperature, performingcooling at a temperature for transition acceleration that is lower thanthese predetermined temperatures by means of the temperature controller,or, at the time of a transition from a low-temperature predeterminedtemperature to a high-temperature predetermined temperature, byperforming heating at a temperature for transition acceleration that iseven higher than these predetermined temperatures for example. The“predetermined time” is the time necessary for maintaining therespective temperatures, and although it depends on the type of theamplification method, the reagents and the amount of liquid used in thePCR method, and the shape, the material, the size, the thickness, andthe like, of the nozzles, a single cycle is, in total, from severalseconds to several 10 seconds for example, and the processing time forthe PCR method as a whole is of the order of approximately severalminutes to several 10 minutes for example. The transition time is alsoincluded in the predetermined time.

Examples of the “mount transfer mechanism” include mechanisms wherebythe intervals between the reaction containers, that is to say, betweenthe stage on which the reaction containers are provided and themeasurement mount are relatively adjustable in the vertical direction ofthe measurement mount and within the horizontal plane for example.Examples of the movement within the horizontal plane include an XY axistransfer mechanism that performs movement of the stage or themeasurement mount along the X axis and the Y axis, or a Y (X) axistransfer mechanism that performs movement along the Y axis or the X axisonly. Examples of the movement of the measurement mount in the axialdirection include a vertical transfer mechanism that moves themeasurement mount in the Z axis direction thereof. This is determinedbased on the arrangement of the coupling ends provided to themeasurement mount or the shape of the stage.

Here, the “measurement control portion” comprises a computer (CPU) builtinto the automatic response/light measurement device, and a program thatdrives the computer. Measurement control is achieved by transmittingsignals through a DA converter to the respective control parts thatdrive the transfer mechanism for example.

The “coupling end” is directly joinable to the aperture of the reactioncontainer, or indirectly joinable via the sealing lid and the like, andis one also having a light guide portion that is able to guide the lightbased on the optical state within the reaction container. The couplingend is a plate-shaped section of the measurement mount, and the lightguide portion represents a hole piercingly provided in the plate-shapedsection thereof, a transparent section, or an optical element such as alens for example. In that case, the coupling end is directly orindirectly joined by adhesion to the aperture of the reaction container,or by directly fitting with the outer periphery of the aperture of thereaction container or by indirectly fitting via the sealing lid and thelike. Alternatively, the coupling end represents a member of acylindrical shape and the like that is provided such that it downwardlyprotrudes from the measurement mount, and is directly joined by beinginserted into the interior of the reaction container or indirectlyjoined via the sealing lid, and the light guide portion is one providedwith a transparent section, such as a cavity provided to the member of acylindrical shape and the like, or an optical fiber, or an opticalelement, such as a lens. There is a case where the light guide portioncomprises separate light guide portions for irradiation and receivinglight. In a case where the coupling end is directly joined to thereaction container, it is preferable to form the reaction container suchthat it is sealable.

The “light guide portions of the coupling ends and the light guideportion of the measuring end are successively optically connected”represents that the light guide portions that penetrate the couplingends and the light guide portion of the measuring end of the measuringdevice are optically connected by becoming opposed at a close proximity.Since the amount of light received by the measuring device at the momentof connection corresponds to a maximum value, the measurement controlportion specifies the data to be measured by calculating the maximumvalue of the amount of light.

The “measuring device” is one that makes fluorescence andchemiluminescence measurements possible for example, and in the formercase, it has a filter for the irradiation of one or two or more types ofexcitation light and the receiving of fluorescent light having one ortwo or more types of wavelengths. In addition, it is preferable forthese to be guided using an optical fiber. The “measuring end” has, atthe very least, an inlet for the light to be received provided in themeasuring device, and in a case of a fluorescence measurement, has anoutlet for the light to be irradiated.

The “on-mount measuring end transfer mechanism” is a mechanism thatoptically successively connects the light guide portions of the couplingends and the light guide portion of the measuring end by continuously orintermittently moving the measuring end on the mount along the movementpath passed by the coupling ends. There is a case where the measuringend and the measuring device body are integrally formed, and a casewhere the measuring end and the measuring device body are connected by aflexible light guide path, such as an optical fiber. In the former case,the on-mount measuring end transfer mechanism moves the measuring deviceas a whole, including the measuring end. In the latter case, only themeasuring end is moved, and the measuring device as a whole is immobilefor example.

It is necessary for the movement of the measuring end by the on-mountmeasuring end transfer mechanism to be performed such that the receivingof the light from all of the reaction containers to be measured iscompleted within the stable light receivable time. Here, the “stablelight receivable time” represents the time in which the optical statewithin the reaction containers, for which the light is receivable, isstably maintained. In the case of the intercalation method or the LUXmethod of real-time PCR, or the TaqMan probe of the hybridization methodfor example, it corresponds to the time in which the elongation reactionof the respective cycles of PCR is performed. In a case where a FRETprobe is used in the hybridization method, it corresponds to the time inwhich annealing is performed.

If the time taken for a single cycle is made several 10 seconds orseveral minutes for example, the stable light receivable time becomesseveral seconds. However, the fluorescent light detection amount of theinitial cycles of a PCR reaction is below the detection limit, and thelater cycles of the PCR reaction become a plateau state, and in order tosecure quantitativeness by a strict definition, it must be within arange of the amplification curve in which an exponential PCRamplification can be observed. The present invention is one in which thestable light receivable time utilizes the fact that the movement time ofthe measuring end between the reaction containers can be used, and byperforming the movement of the measuring end necessary for receiving thelight from the respective reaction containers within the stable lightreceivable time, the receiving of the light from the plurality ofreaction containers can be performed approximately in parallel by meansof a single measuring device, or a sufficiently small number incomparison to the number of reaction containers, without using acomplicated optical system and without expanding the scale of thedevice.

Since it is “a measuring end having at least one light guide portion”,the measuring end can be made to have two light guide portions that arerespectively connectable to the two light guide portions of the couplingends aligned in a direction perpendicular to the movement direction ofthe measuring end, and be used as a single measuring device byswitchingly guiding the light for example.

The “optical state” represents a state such as light emissions, colors,color changes, or light variations. The light based on the optical staterepresents light from light emissions or light variations, or reflectedlight from light irradiated with respect to colors or color changes, ortransmitted light, scattered light and the like.

A second aspect of the invention is an automatic response/lightmeasurement device, wherein the measuring device has a plurality oftypes of specific wavelength measuring devices capable of receivinglight of specific wavelengths or specific wavelength bands, each ofwhich has a measuring end having at least one light guide portion thatis optically connected to said light guide portion of the coupling ends,and a measuring end bundling portion that bundles in parallel theplurality of measuring ends, and the measuring ends are movable inparallel on the mount by means of the on-mount measuring end transfermechanism, and the measurement control portion, by means of the movementof the measuring ends, controls the on-mount measuring end transfermechanism such that the light guide portions of the coupling ends andthe light guide portions of the measuring ends of the specificwavelength measuring devices are successively optically connected.

Here, in a case where fluorescent light is measured, it is necessary toprovide the measuring device or the specific wavelength measuringdevices with an excitation light irradiation portion that irradiates acorresponding excitation light in addition to the light receivingportion. The measuring ends of the measuring device, which are opticallyconnectable to the light guide portions of the coupling ends, areprovided with a cavity, an optical element such as a lens, or a lightguide path such as an optical fiber for example.

The “joining” is integrally or linkingly performed. “Integrally”represents joining such that the intervals between the measuring endsare mutually fixed and do not have any degrees of freedom. “Linkingly”represents joining such that the intervals between the measuring endshave degrees of freedom to some extent, such as in a chain. Furthermore,“in parallel” refers to a state in which the coupling ends are alignedin the order of joining along the same movement path that is set on themount or on the container group.

According to the present aspect of the invention, by using a pluralityof types of luminescent compounds, colored compounds, color changingcompounds, or light variation compounds and performing amplificationprocessing in parallel under the same conditions on a plurality of typesof amplification subjects in a single reaction container, it is possibleto perform multiplex PCR amplification or multiplex real-time PCR on aplurality of types of amplification subjects by using a primer labeledwith a plurality of types of luminescent compounds for example.

Since it is “light of a specific wavelength or a specific wavelengthband”, it represents, in terms of visible light, a range of wavelengthssuch as a red light, a yellow light, a green light, a blue light or aviolet light for example.

A third aspect of the invention is an automatic response/lightmeasurement device, wherein the container group has sealing lids whichhave transparency, that are mounted on the apertures of the reactioncontainers and seal the reaction containers, the sealing lids arejoinable with the coupling ends, and the measurement control portioncontrols the mount transfer mechanism such that the mount is moved sothat the sealing lids are mounted on the coupling ends, and the couplingends are indirectly joined with the apertures of the reaction containersvia the sealing lids.

Here, the “sealing lid” includes, in addition to those that areinflexible and a plate form or block form, those that are a film form ora membrane form and have a flexibility. The “mounting” includes fitting,threading, friction, adsorption, attachment, adhesion, and the like. Inthese cases, detachable mounting is preferable.

A fourth aspect of the invention is an automatic response/lightmeasurement device, wherein the mount transfer mechanism makes the mountrelatively movable in a vertical direction with respect to the containergroup, and the measurement control portion, after controlling the mounttransfer mechanism to indirectly join the coupling ends via the sealinglids such that they cover the apertures of the reaction containers,performs control such that it presses or shakes the sealing lidscovering the apertures.

It is preferable for the coupling ends to be provided such that theydownwardly protrude from the mount. In this case, the coupling ends, forexample, have a shape such as a rod shape, a cylinder shape, a coneshape, and the like, and the lower end portions of the members are ableto make contact with the sealing lids. The pressing or the shaking isperformed by the transfer mechanism that moves the mount, which islinked with the coupling ends, along the Z axis for example.

A fifth aspect of the invention is an automatic response/lightmeasurement device having a heating portion that is able to heat thecoupling ends.

Here, the heating of the coupling ends by the heating portion isperformed for preventing direct or indirect condensation on the couplingends at the time of temperature control of the reaction containers,which are directly or indirectly sealed by the coupling ends. Themeasurement control portion or the nucleic acid processing controller,following controlling the mount transfer mechanism such that thecoupling ends are simultaneously directly or indirectly joined with theapertures of the two or more reaction containers, controls the heatingportion such that direct or indirect condensation on the coupling endsis prevented. “Preventing direct or indirect condensation on thecoupling ends” represents prevention of condensation on the end portionsof the coupling ends themselves, and “preventing indirect condensation”represents preventing condensation on the sealing lids mounted on thecoupling ends. Here, the “heating portion” is sufficient if it has aheating function at a temperature that is set based on the magnitude ofan applied electric current or by an ON/OFF control.

A sixth aspect of the invention is an automatic response/lightmeasurement device having; a temperature controller that performstemperature control of the interior of the reaction containers by havinga temperature source provided such that, with respect to the reactioncontainers having a lower side wall section and an upper side wallsections positioned further on the upper side than the lower side wallsection, it is able to make contact with or approach the lower side wallsections, and a heating portion provided such that it is able to makecontact with or approach the upper side wall sections, and that has aheat source that is able to heat the upper side wall sections.

Here, the “lower side wall section” represents a wall section or aportion thereof including the bottom portion that encloses a volumesection, which is a portion (1% to 90% for example) of the entire volumeof the reaction container in which a predetermined rated liquid amountis housed. The lower side wall section represents a section of the wallsection from the liquid surface of the housed rated volume of liquid tothe bottom portion for example. In a case where the reaction containerscomprise a wide-mouthed piping part, to which the coupling ends aremounted, and a narrow-mouthed piping part, it is provided on thenarrow-mouthed piping part. The “upper side wall section” represents,within the entire volume of the reaction container, a container sectionenclosing the remaining volume of the lower side container section, inwhich the rated liquid amount is housed, or a portion thereof. The“upper side wall section” is normally preferably provided leaving aspacing with the lower side wall section, and on the upper side in thevertical direction. The upper side wall section is closer to theaperture than the lower side wall section, although it is provided onthe lower side of the section on which the coupling end is mounted. Inthe case of the container comprising the wide-mouthed piping part andthe narrow-mouthed piping part, it is provided on the narrow-mouthedpiping part for example. The upper side wall section is preferablyprovided as a band shape along the circumference of the container wallfor example.

The measurement control portion, following controlling the mounttransfer mechanism such that the coupling ends are simultaneouslydirectly or indirectly joined with the apertures of the reactioncontainers, controls the heating portion such that direct or indirectcondensation on the coupling ends is prevented. “Indirectly joined”represents a case where the coupling ends are joined with the reactioncontainers via the sealing lids. “Control of the heating portion” isperformed according to the “temperature control” for preventingcondensation. The heating temperature is set to a temperature amongtemperatures (a temperature necessary for preventing condensation thatexceeds the dew point temperature of water vapor but is a temperaturethat is sufficiently lower than the melting point of the raw material ofthe reaction container. These are determined by the volume, the shape orthe raw material of the reaction container, the pressure or the humiditywithin the reaction container, the content of the temperature controlincluding the predetermined temperature, the liquid amount, thecomposition of the solution, the temperature, the pressure, theprocessing aims and the like) that are from several degrees to severalten degrees higher than the respective predetermined temperatures set bythe temperature control for example. It is controlled such that it isset from 1° C. to 60° C., or preferably of the order of approximately 5°C. higher than the predetermined temperature for example. In a casewhere the amplification is by PCR for example, heating is performed in aconstant temperature state at the maximum predetermined temperature,namely a temperature several degrees higher than 94° C., such as 100° C.Alternatively, heating is performed such that it follows temperaturesthat are several degrees higher than the respective predeterminedtemperatures corresponding to the temperature control. Furthermore, inan isothermal case, in a case where the predetermined temperature isapproximately 55° C., heating is performed at a temperature that isseveral degrees higher for example, namely from 60° C. to 70° C.

As a result of the heating portion performing heating with respect tothe reaction containers rather than the coupling ends, thermal effectstoward the optical system elements provided to the coupling ends or themeasuring ends in the proximity of the coupling ends are reduced, andthe degradation of the optical system elements such as prisms, opticalfibers, various lenses such as rod lenses, mirrors, and waveguide tubes,can be prevented, or the reliability of the images obtained via theoptical system elements can be increased.

A seventh aspect of the invention is an automatic response/lightmeasurement device, wherein the measurement mount is provided to anozzle head having a suction-discharge mechanism that performs suctionand discharge of gases, and one or two or more nozzles that detachablymount dispensing tips in which the suction and the discharge of liquidsis possible by means of the suction-discharge mechanism, and the mounttransfer mechanism has a nozzle head transfer mechanism that makes thenozzle head relatively movable between the container groups.

In this case, in addition to further providing a magnetic force partthat is able to apply or remove a magnetic force within the dispensingtips mounted on the nozzles or liquid housing parts provided in thecontainer group, and which is able to adsorb the magnetic particles onan inner wall of the dispensing tips or the liquid housing parts, it ispreferable to provide an extraction control part that controls thesuction-discharge mechanism, the transfer mechanism, and the magneticforce part, and as the reaction solution, separates and extracts thesolution of the amplification subject from the sample and houses itwithin the liquid housing parts as a portion of the amplificationsolution.

Here, the “solution for separating and extracting” includes a dissolvingsolution that breaks down or dissolves the protein forming the cellwalls and the like contained in the sample and discharges the nucleicacids or the fragments thereof to the outside of the bacteria or thecell, a buffer solution that simplifies the capture of the nucleic acidsor the fragments thereof by the magnetic particles, and additionally, asolution that dissociates from the magnetic particles, the nucleic acidsor the fragments of nucleic acids captured by the magnetic particles. Inorder to perform the separation of the nucleic acids or the fragmentsthereof, it is preferable to repeat the suction and the discharge of themixed solution.

The “dispensing tip” comprises for example a thick diameter portion, anarrow diameter portion, and a transition portion that communicatesbetween the thick diameter portion and the narrow diameter portion. Thethick diameter portion has an aperture for mounting, into which thelower end of the nozzle is inserted and the nozzle is mounted, and thenarrow diameter portion has an end mouth portion in which liquids canflow in and flow out by means of the suction and discharge of gases bythe suction-discharge mechanism. The dispensing tip and the nozzle aremanufactured from organic substances such as resins of polypropylene,polystyrene, polyester, acrylic, and the like, and inorganic substancessuch as glass, ceramics, metals including stainless steel, metalcompounds, and semiconductors.

The “suction-discharge mechanism” is for example a mechanism formed by acylinder, a piston that slides within the cylinder, a nut portion joinedto the piston, a ball screw on which the nut portion is threaded, and amotor that rotatingly drives the ball screw in both forward and reversedirections.

In a case where two or more nozzles are used, by respectively arrangingtwo or more container groups so as to correspond to the respectivenozzles within two or more exclusive regions corresponding to therespective nozzles, in which a single nozzle enters and the othernozzles do not enter, and by setting the respective exclusive regionsfor each different sample, cross-contamination between samples can beprevented with certainty.

An eighth aspect of the invention is an automatic response/lightmeasurement device, wherein the container group comprises two or moreexclusive regions corresponding to the nozzles of the respective groups,which comprise one or two or more nozzles, in which nozzles of a singlegroup enter and the nozzles of other groups do not enter, and therespective exclusive regions at the very least have at least onereaction container, one or two or more liquid housing parts that housereaction solutions used in the reactions, and sealing lids that aretransportable to the reaction containers using the coupling ends and areable to seal the reaction solutions housed in the reaction containers,and the mount is extendingly provided across all of the exclusiveregions such that the coupling ends of the measurement mount areassociated such that coupling ends of a single group, which comprisesone or two or more coupling ends, enter the respective exclusive regionsand the coupling ends of other groups do not enter.

In order to make “the nozzles of a single group enter and the nozzles ofthe other groups not enter” or “the coupling ends of a single groupenter and the coupling ends of the other groups not enter”, for example,this is performed by providing an exclusive region control part thatcontrols the nozzle head transfer mechanism such that nozzles of asingle group enter the respective exclusive regions and the nozzles ofthe other groups do not enter, and controls the measuring devicetransfer mechanism such that the coupling ends of a single group enterthe respective exclusive regions and the coupling ends of the othergroups do not enter.

A ninth aspect of the invention is an automatic response/lightmeasurement device comprising: a nozzle head provided with asuction-discharge mechanism that performs suction and discharge ofgases, and one or two or more nozzles that detachably mount dispensingtips in which the suction and the discharge of liquids is possible bymeans of the suction-discharge mechanism; a container group having atthe very least one or two or more liquid housing parts that housereaction solutions used for various reactions, a liquid housing partthat houses a magnetic particle suspension in which magnetic particlesthat are able to capture a target compound are suspended, a liquidhousing part that houses a sample, one or two or more liquid housingparts that house a solution for separating and extracting of the targetcompound, and two or more reaction containers; a nozzle head transfermechanism that makes an interval between the nozzle head and thecontainer group relatively movable; a magnetic force part that is ableto adsorb the magnetic particles on an inner wall of the dispensing tipsmounted on the nozzles; a measurement mount provided to the nozzle head,and provided with two or more coupling ends that are directly orindirectly joinable with the apertures of the reaction containers, andhave light guide portions that optically connect with the interior ofthe joined reaction containers; a measuring device provided on themount, that has measuring ends having light guide portions thatoptically connect with the light guide portions of the coupling ends,and is able to receive light based on an optical state within thereaction container via the measuring ends; an on-mount measuring endtransfer mechanism that makes the measuring ends movable on the mount;and a magnetic force part that is able to apply or remove a magneticforce that is able to adsorb the magnetic particles on an inner wall ofthe dispensing tips mounted on the nozzles; and has a separation andextraction control that, at the very least, controls thesuction-discharge mechanism, the nozzle head transfer mechanism, and themagnetic force part and controls the separation and the extraction ofthe target compound; and a measurement control portion that, at the veryleast, controls the suction-discharge mechanism and the nozzle headtransfer mechanism, and following movement of the mount such that thecoupling ends simultaneously directly or indirectly join with theapertures of the two or more reaction containers, and following controlof the on-mount measuring end transfer mechanism and movement of themount such that the coupling ends simultaneously directly or indirectlyjoin with the apertures of the two or more reaction containers, controlsthe on-mount measuring end transfer mechanism such that the light guideportions of the coupling ends and light guide portions of the measuringends are successively optically connected, and instructs a measurementby the measuring device.

Here, the “reaction solution” is for example an amplification solutionused for nucleic acid amplification. Furthermore, the “target compound”represents nucleic acids or the fragments thereof, which is theamplification subject. It is preferable to provide a lid detachingmechanism that detaches the sealing lids from the coupling ends, or atip detaching mechanism that detaches the dispensing tips from thenozzles. In the present device, it is preferable to provide a samplesupplying device having a dispensing function that supplies the samples,the reagents, the washing liquids, the buffers, and the like that arenecessary for the container group at a position separate to the stage ofthe automated reaction/light device, and to make the whole stage, towhich the supplied container group is built-in, be automatically movedto the position of the stage of the automatic response/light measurementdevice and to be made exchangeable. Consequently, processing, includingpreparation processing such as the dispensing processing or thesupplying processing with respect to the container group, can beconsistently performed.

A tenth aspect of the invention is an automatic response/lightmeasurement device, wherein the measuring device has a plurality oftypes of specific wavelength devices capable of receiving light ofspecific wavelengths or specific wavelength bands, each of which has ameasuring end having at least one light guide portion that is opticallyconnected to said light guide portions of the coupling ends, and ameasuring end bundling portion that bundles the interval between theplurality of measuring ends in parallel, and the measuring ends aremovable in parallel on the mount by means of the on-mount measuring endtransfer mechanism, and the measurement control portion controls theon-mount measuring end transfer mechanism such that, by means of themovement of the measuring ends, the light guide portions of the couplingends and the light guide portions of the measuring ends of the specificwavelength measuring devices are successively optically connected.

An eleventh aspect of the invention is an automatic response/lightmeasurement device, wherein the container group has sealing lids whichhave transparency and are able to seal the reaction containers byfitting with the apertures of the reaction containers, the sealing lidsare mountable on the coupling ends, the measuring device is able toreceive light based on an optical state within the reaction containersvia the coupling ends and the sealing lids, and in addition, further hasa sealing control part that controls the nozzle head transfer mechanismsuch that the sealing lids are simultaneously mounted on the couplingends, and the measurement control portion, following control of thenozzle head transfer mechanism such that the coupling ends aresimultaneously joined with the apertures of the reaction containersindirectly via the sealing lids, controls the on-mount measuring endtransfer mechanism such that the light guide portions of the couplingends and light guide portions of the measuring ends are successivelyoptically connected.

A twelfth aspect of the invention is an automatic response/lightmeasurement device further having a mount Z axis transfer mechanism thatmakes the measurement mount provided to the nozzle head movable in thevertical direction with respect to the nozzle head, and further having apressing and the like control part that, following control of the mountZ axis transfer mechanism and indirectly joining the coupling ends withthe apertures of the reaction containers, performs control such that thesealing lids covering the apertures are pressed or shaken. Here, the“mount Z axis transfer mechanism” is one provided separately to the“nozzle head transfer mechanism”.

A thirteenth aspect of the invention is an automatic response/lightmeasurement device having a heating portion that is able to heat thecoupling ends.

Here, the heating portion, after the sealing lids are simultaneouslymounted on the coupling ends and following control of the mount transfermechanism such that the coupling ends are simultaneously indirectlyjoined with the apertures of the two or more reaction containers, iscontrolled by the measurement control portion or the nucleic acidprocessing controller such that it heats the sealing lids via thecoupling ends.

A fourteenth aspect of the invention is an automatic response/lightmeasurement device having: a temperature controller having a temperaturesource which is provided such that, with respect to the reactioncontainer having a lower side wall section and an upper side wallsection positioned further on the upper side of the lower side wallsection, it is able to make contact with or approach the lower side wallsections, and that performs temperature control of the interior of thereaction containers; and a heating portion which is provided such thatit is able to make contact with or approach the upper side wallsections, and that has a heat source that is able to heat the upper sidewall sections.

The heating portion, following control of the mount transfer mechanismby means of the rated control part or the nucleic acid processingcontroller such that the coupling ends are simultaneously directly orindirectly joined with the apertures of the reaction containers, iscontrolled such that, at the time of temperature control by means of thetemperature controller, direct or indirect condensation on the couplingends is prevented.

A fifteenth aspect of the invention is an automatic response/lightmeasurement device, wherein the container group comprises, two or moreexclusive regions corresponding to the nozzles of the respective groups,which comprise one or two or more nozzles, in which nozzles of a singlegroup enter and the nozzles of other groups do not enter, and therespective exclusive regions at the very least have at least onereaction container, one or two or more liquid housing parts that housereaction solutions used in the reactions, a liquid housing part thathouses a magnetic particle suspension in which magnetic particles thatare able to capture a target compound are suspended, a liquid housingpart that houses a sample, two or more liquid housing parts that house asolution for separating and extracting of the target compound, andsealing lids that are transportable to the reaction containers using thecoupling ends and are able to seal the reaction solutions housed in thereaction containers, the mount is extendingly provided across all of theexclusive regions such that the coupling ends of the measurement mountare such that the coupling ends of a single group which comprises one ortwo or more coupling ends, enter each of the respective exclusiveregions, and the coupling ends of other groups do not enter, the nozzlehead transfer mechanism is controlled such that the nozzles of a singlegroup enter the respective exclusive regions and the nozzles of theother groups do not enter, and there is further provided an exclusiveregion control part that controls the on-mount measuring end transfermechanism such that the coupling ends of a single group enter therespective exclusive regions and the coupling ends of the other groupsdo not enter.

A sixteenth aspect of the invention is an automatic response/lightmeasurement method, that performs measurement by; moving a measurementmount to which two or more coupling ends having light guide portions areprovided, with respect to apertures of two or more reaction containersarranged in a container group, directly or indirectly simultaneouslyjoining the apertures of the reaction containers and the coupling ends,and optically connecting the interior of the joined reaction containersand the light guide portions provided to the coupling ends, performingtemperature control within the reaction containers, moving the measuringends provided to the measuring device on the mount, so that the lightguide portions provided to the coupling ends and the light guideportions of the measuring ends are successively optically connected, andmaking the measuring device receive light based on an optical statewithin the reaction containers, via the measuring ends.

A seventeenth aspect of the invention is an automatic response/lightmeasurement method, wherein a plurality of types of specific wavelengthmeasuring devices that are able to receive light of specific wavelengthsor specific wavelength bands at the time of the measurement are providedas the measuring device, and the light guide portions of measuring endsof the specific wavelength measuring devices are optically connectedwith the light guide portions of the coupling ends and are able toreceive light of specific wavelengths or specific wavelength bands basedon an optical state within the reaction containers via the measuringends, and measurement is performed by bundling the measuring ends of theplurality of types of specific wavelength measuring devices and movingthese on the mount in parallel, to thereby successively opticallyconnected the light guide portions provided to the coupling ends andlight guide portions of the measuring ends, and making the specificwavelength measuring devices receive light of specific wavelengths orspecific wavelength bands based on the optical state within the reactioncontainers, via the measuring ends.

An eighteenth aspect of the invention is an automatic response/lightmeasurement method that moves the mount with respect to two or moresealing lids which have transparency, that are arranged in the containergroup and are fittable with the apertures of the reaction containers,and moves the mount with respect to the apertures of the reactioncontainers following simultaneous mounting of the sealing lids on thecoupling ends.

A nineteenth aspect of the invention is an automatic response/lightmeasurement method that, following mounting of the reaction containerson the measurement mount, performs pressing or shaking with respect tothe sealing lids covering the apertures of the reaction containers.

A twentieth aspect of the invention is an automatic response/lightmeasurement method, that performs measurement by: detachably mountingdispensing tips on nozzles provided to nozzle heads, which performsuction and discharge of gases, separating a target compound using; anozzle head transfer mechanism that relatively moves between a magneticforce part, the nozzle head, and a container group, a magnetic particlesuspension in which magnetic particles that are able to capture thetarget compound housed in the container group are suspended, a sample,and a solution for separating and extracting of the target compound,introducing the separated target compound and a reaction solution usedfor a reaction into a plurality of reaction containers provided to thecontainer group, moving at the very least by means of the nozzle headtransfer mechanism, a measurement mount that, in addition to beingprovided to the nozzle head, is provided with two or more coupling endshaving light guide portions, with respect to apertures of the reactioncontainers, directly or indirectly simultaneously joining the aperturesof the reaction containers and the coupling ends, and opticallyconnecting the interior of the joined reaction containers and the lightguide portions provided to the coupling ends, performing temperaturecontrol within the reaction containers, moving the measuring endsprovided to the measuring device on the mount, so that the light guideportions of the coupling ends and the light guide portions of themeasuring ends are optically successively connected, and making themeasuring device receive light based on an optical state within thereaction containers, via the measuring ends.

A twenty-first aspect of the invention is an automatic response/lightmeasurement method, wherein at the time of directly or indirectlyjoining the apertures of the reaction containers and the coupling ends,and performing temperature control within the reaction containers,condensation on the coupling ends is directly or indirectly prevented bya heat source positioned further on an upper side than a lower side wallsection of the reaction container and provided making contact with orapproaching an upper side section of the reaction container, accordingto temperature control of a temperature source provided making contactwith or approaching the lower side wall section.

A twenty-second aspect of the invention is an automatic response/lightmeasurement device comprising: a container group in which two or morereaction containers are arranged; a plurality of types of specificwavelength measuring devices provided with measuring ends having lightguide portions that are optically connectable with the interior of thereaction containers, and that are able to receive light of specificwavelengths or specific wavelength bands based on an optical statewithin the reaction containers via the measuring ends; a measuring endbundling portion that bundles the plurality of measuring ends inparallel; a measuring end transfer mechanism that makes the bundledmeasuring ends relatively movable with respect to the container group;and a measurement control portion that, by moving the measuring endsalong a movement path that successively passes apertures of the reactioncontainers, controls the measuring end transfer mechanism such thatlight guide portions of the measuring ends and the interior of thereaction containers are successively optically connected, and, withrespect to the specific wavelength measuring devices, instructs ameasurement by receiving light of the specific wavelengths or specificwavelength bands based on an optical state within the reactioncontainers. Here, the “measuring end transfer mechanism” corresponds tothe mount transfer mechanism and the on-mount measuring end transfermechanism.

A twenty-third aspect of the invention is an automatic response/lightmeasurement device further comprising a measurement mount provided withtwo or more coupling ends that are directly or indirectly joinable withthe apertures of the reaction containers, and that have light guideportions that optically connect with the interior of the joined reactioncontainers, wherein the measuring ends of the specific wavelengthmeasuring device are provided on the mount, and in addition, themeasuring end transfer mechanism has a mount transfer mechanism thatmakes the mount relatively movable with respect to the container group,and an on-mount measuring end transfer mechanism that makes themeasuring ends of the specific wavelength measuring device movable inparallel on the mount.

A twenty-fourth aspect of the invention is a reaction container controlsystem comprising: a reaction container, a temperature controller that,with respect to the reaction container having a lower side wall sectionof the reaction container and an upper side wall section positioned onan upper side of the lower side wall section, has a temperature sourceprovided such that it is able to make contact with or approach the lowerside wall section, and that performs temperature control within thereaction container; and a heating portion that is provided such that itis able to make contact with or approach the upper side wall section,and that has a heat source that is able to heat the upper side wallsection.

The heating portion is such that the heating portion is controlled sothat the condensation on the member for light measurement mounted on theaperture of the reaction container is prevented. Here, the “member forlight measurement” represents a member for measurement that measures theoptical state within the reaction container, and includes; a sealing lidwhich has transparency and that is mounted on the aperture of thereaction container, the coupling end, the end portion of an opticalfiber, a waveguide tube, various lenses such as a rod lens, a mirror, anoptical system element such as a prism, or a member in which these arebuilt-in.

A twenty-fifth aspect of the invention is a reaction container controlsystem, wherein the reaction container comprises a wide-mouthed pipingpart, and a narrow-mouthed piping part that is formed narrower than thewide-mouthed piping part and is provided on a lower side of thewide-mouthed piping part and communicated with the wide-mouthed pipingpart, a member for light measurement is mountable on the wide-mouthedpiping part, liquids are housable in the narrow-mouthed piping part, andthe lower side wall section and the upper side wall section are providedto the narrow-mouthed piping part.

Effects of the Invention

According to the first aspect of the invention, the ninth aspect of theinvention, the sixteenth aspect of the invention, the twentieth aspectof the invention or the twenty-third aspect of the invention, by joiningthe apertures of the plurality of reaction containers and the couplingends provided to the measurement mount, the interval between theplurality of reaction containers and the measurement mount is integratedand the positional relationship is fixed, and the light guide portionsprovided to the coupling ends are smoothly optically connected with thereaction containers in a state in which subtle displacements or relativemovements that occur at the time of positioning in a case where they areseparated are excluded, and it is possible to guide the light of theoptical state of the central sections of the reaction containers to themeasuring device mounted on the measurement mount. Further, with respectto the plurality of reaction containers that are correctly positionedvia the measurement mount, by moving the measuring device continuouslyor intermittently such that the measuring end of the measuring deviceset on the measuring mount passes a predetermined path, such as a linearpath, that passes the end portions of the light guide portions on themount, the light guide portions of the coupling ends and the light guideportions of the measuring ends of the measuring device are successivelyoptically connected with certainty, and the measurement can be performedby receiving the light from the fixed position of the reaction containerwith a high accuracy. The measurement result and the amplification curvefrom real-time PCR are created, and can be utilized in various analyses,such as the determination of the initial concentration of DNA.

Furthermore, since the measurement of the plurality of reactioncontainers can be performed with a single measuring device by utilizingthe stable light receivable time, the expansion of the scale of thedevice is suppressed, and the manufacturing costs can be reduced.Moreover, since it is possible to measure by successively moving theupper ends of the light guide portions of the coupling ends joined withthe reaction containers, through the shortest distance along thepredetermined path passed by the measuring ends, a light switchingmechanism and the like is not necessary, and the measurements can beperformed in parallel by a simple mechanism of only a transfer mechanismbetween the plurality of reaction containers.

Since the reactions and the measurements are performed by sealing thereaction containers by joining the apertures of the reaction containerswith joined portions, automatic measurements with a high reliability inwhich cross-contaminations can be prevented with certainty can beperformed.

According to the second aspect of the invention, the tenth aspect of theinvention, the seventeenth aspect of the invention, the twenty-secondaspect of the invention, or the twenty-third aspect of the invention, byusing a plurality of types of luminescent compounds, colored compounds,color changing compounds, or light variation compounds, within a singlereaction container, then for example in a case where amplificationprocessing is performed in parallel under the same conditions on aplurality of types of amplification subjects, it is possible to performmultiplex PCR amplification or multiplex real-time PCR on a plurality oftypes of amplification subjects by using a primer labeled with aplurality of types of luminescent compounds and the like. At that time,by combining the switching of the receiving of the light of a pluralityof types of specific wavelengths or specific wavelength bands from theplurality of types of luminescent compounds and the like, with amechanism utilizing the stable light receivable time that is used at thetime of movement between the plurality of reaction containers, it is notnecessary to separately provide a special light switching mechanism, andthe device mechanism can be simplified and manufacturing costs can bereduced. Furthermore, since the respective specific wavelength measuringdevices each receive light of a specific wavelength or a specificwavelength band, the effects of other specific wavelengths or specificwavelength bands are not received, and high-accuracy measurements can beperformed. Moreover, since the respective specific wavelength measuringdevices are each modularized such that removal and addition can beperformed, processing with a high versatility according to theprocessing aims can be performed. In the case of the second aspect ofthe invention, the tenth aspect of the invention, the seventeenth aspectof the invention, or the twenty-third aspect of the invention, since themeasuring device is moved following joining of the apertures of thereaction containers with the coupling ends, and the integration of thereaction containers and the mount, the receiving of light can beperformed with a high accuracy.

According to the third aspect of the invention, the eleventh aspect ofthe invention, or the eighteenth aspect of the invention, by mountingthe sealing lids arranged in the container group on the coupling ends,it is possible to perform mounting to the apertures of the reactioncontainers by means of the movement of the measurement mount. Thereforethe housed substances within the reaction containers do not make directcontact with the coupling ends of the mount, and hencecross-contaminations can be effectively prevented. Furthermore, since itis not necessary to provide a dedicated mechanism for mounting thesealing lid on the reaction containers, the scale of the device is notexpanded, and the manufacturing costs are reduced.

According to the fourth aspect of the invention, the twelfth aspect ofthe invention, or the nineteenth aspect of the invention, the sealing ofthe reaction containers can be performed with certainty by controllingthe sealing lids covering the apertures of the reaction container suchthat they are pressed. Furthermore, by shaking the sealing lids, thesealed state between the apertures of the reaction container and thesealing lids can be rapidly and easily removed and released. Therefore,a high processing efficiency and reliability can be obtained.

According to the fifth aspect of the invention, or the thirteenth aspectof the invention, by performing control such that the coupling ends areheated, condensation at the time of temperature control of the reactioncontainers that are directly or indirectly sealed by the coupling endsis prevented, and measurements via the coupling ends or the sealing lidswhich have transparency, can be performed with certainty and a highaccuracy.

According to the sixth aspect of the invention, the fourteenth aspect ofthe invention, or the twenty-first aspect of the invention, byperforming control of the heating of the coupling end making direct orindirect contact by means of the lower side wall sections of thereaction containers, and therefore the temperature control of lower sidewall section, and in addition, the heating control of the upper sidewall sections of the reaction containers, direct or indirectcondensation on the coupling ends can be prevented. Then, the couplingends are not directly heated, and since the heating is performed at theupper side wall sections of the reaction containers, the direct effectsof heating toward the optical system elements provided to the couplingends can be reduced. Consequently, in addition to reducing or removingimage distortions and the like from the degradation or the change inproperties of the optical system elements, by performing temperaturecontrol such that, according to the heating, the temperatures of thelower side wall sections are guided to the respective predeterminedtemperatures set using a coolable Peltier element and the like,measurements with a high reliability can be performed. Further, sincevarious optical system elements can be provided to the coupling ends,precise measurements with a high versatility can be performed.Furthermore, since the prevention of direct or indirect condensation onthe coupling ends is achieved by heating the wall sections of thereaction containers, it is not necessary to provide a heating portiondirectly above the containers, and the structure directly above thecontainers, and therefore the structure of the device as a whole issimplified, and it is possible to further approach the coupling endspossessing optical system elements, to the containers and to perform theoptical measurements with certainty.

According to the seventh aspect of the invention to the ninth aspect ofthe invention, the fifteenth aspect of the invention, or the twentiethaspect of the invention, as a result of the measurement mount beingbuilt into the nozzle head to which the nozzles are provided, a transfermechanism (at the very least the X axis and Y axis directions) betweenthe reaction containers of the measuring device is not separatelyprovided, and since it can be combined with the transfer mechanism ofthe nozzles, the expansion of the scale of the device can be prevented.Furthermore, since the transfer to the reaction container of the samplesolution, the reagent solutions, and the reaction solutions, which areto be housed within the reaction container, and which represent themeasurement subject, and the preparation, can be performed using thefunctions of the nozzles, steps from the processing to the measurementof the measurement subject can be consistently, efficiently, and rapidlyperformed.

According to the twenty-fourth aspect of the invention and thetwenty-fifth aspect of the invention, by performing heating control ofthe upper side wall sections of the reaction containers in addition tothe temperature control of the lower side wall sections of the reactioncontainers, direct or indirect condensation on the member for lightmeasurement for performing optical measurements of the optical statewithin the reaction containers is prevented. Then, the member for lightmeasurement is not directly heated and since heating control of theupper side wall sections of the reaction containers is performed, theeffects of heating toward the optical system elements provided to themember for light measurement can be reduced. Consequently, in additionto reducing or removing image distortions and the like from thedegradation or the change in properties of the optical system elements,by performing temperature control such that, according to the heating,the temperatures of the lower side wall sections are guided to therespective predetermined temperatures set using a coolable Peltierelement and the like, measurements with a high reliability areperformed, and precise measurements with a high versatility can beperformed. Furthermore, since the prevention of direct or indirectcondensation on the member for light measurement is achieved by heatingthe wall sections of the reaction containers, it is not necessary toprovide a heating portion directly above the containers, and thestructure directly above the containers, and therefore the structure ofthe container reaction system as a whole is simplified, and since it ispossible to further approach the member for light measurement possessingoptical system elements, to the containers, optical measurements can beperformed with certainty.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an overall block-diagram showing an automatic response/lightmeasurement device according to a first embodiment of the presentinvention.

FIG. 2 is a perspective view showing a first exemplary embodiment of theautomatic response/light measurement device shown in FIG. 1.

FIG. 3 is a plan view showing enlarged, a container group of theautomatic response/light measurement device shown in FIG. 2.

FIG. 4 is a drawing showing enlarged, a whole nozzle head of theautomatic response/light measurement device shown in FIG. 2.

FIG. 5 is a perspective view showing a case where dispensing tips aremounted on nozzles of the device shown in FIG. 2 to FIG. 4.

FIG. 6 is a cross-sectional view and a perspective view showing a statein which a coupling end is joined to a reaction container shown in FIG.3.

FIG. 7 is a perspective view showing a second exemplary embodiment ofthe automatic response/light measurement device shown in FIG. 1.

FIG. 8 is a plan view showing enlarged, a container group of theautomatic response/light measurement device shown in FIG. 7.

FIG. 9 is a drawing showing a measuring device according to a thirdexemplary embodiment of the present invention.

FIG. 10 is a drawing showing a measuring device according to a fourthexemplary embodiment of the present invention.

FIG. 11 is a drawing showing a measuring device according to a fifthexemplary embodiment of the present invention.

FIG. 12 is an overall block-diagram showing an automatic response/lightmeasurement device according to a second embodiment of the presentinvention.

FIG. 13 is a side view showing enlarged, the whole nozzle head of theautomatic response/light measurement device shown in FIG. 12.

FIG. 14A is a cross-sectional view showing a reaction container controlsystem according to a first exemplary embodiment of the secondembodiment.

FIG. 14B is a cross-sectional view showing a reaction container controlsystem according to a second exemplary embodiment of the secondembodiment.

BEST MODE FOR CARRYING OUT THE INVENTION

Next, an embodiment of the present invention is described with referenceto the drawings. This embodiment is not to be interpreted as limitingthe present invention unless particularly specified. Furthermore, in theembodiments, the same objects are denoted by the same reference symbols,and the descriptions are omitted.

FIG. 1 shows a block-diagram of an automatic response/light measurementdevice 10 according to a first embodiment of the present invention.

The automatic response/light measurement device 10 broadly has: aplurality (twelve in this example) of container groups 20 in whichreaction container groups 23 i (i=1, . . . , 12, omitted hereunder) arearranged; a nozzle head 50 that has a nozzle arrangement portion 70 inwhich a plurality (twelve in this example) of nozzles 71 i thatdetachably mount dispensing tips are arranged, and a measurement mount30; a measuring device 40 provided on the mount 30; a nozzle headtransfer mechanism 51 that makes the nozzle head 50 movable in the Xaxis direction for example; a temperature controller 29 that performspredetermined temperature control with respect to the reaction containergroups 21 i of the container group; a CPU+program 60 composed of a CPU,a ROM, a RAM, various types of external memory, communication functionssuch as a LAN, and a program stored in the ROM, and the like; and acontrol panel 13 having a display portion such as a liquid crystaldisplay, and an operation portion, such as operation keys or a touchpanel.

The nozzle head 50 has: a mount Z axis transfer mechanism 35 that makesthe mount 30 movable in the Z axis direction with respect to thecontainer group 20 independent of the nozzle arrangement portion 70; anozzle Z axis transfer mechanism 75 that makes the nozzle arrangementportion 70 movable in the Z axis direction with respect to the containergroup 20 independent of the mount 30; a magnetic force part 57 that, bymeans of a magnet 571 provided on a narrow diameter portion 211 ia of adispensing tip 211 i detachably mounted on the nozzle 71 i such that itcan approach and separate, is able to apply and remove a magnetic fieldwith respect to the interior; a suction-discharge mechanism 53 thatmakes the suction and the discharge of liquids with respect to thedispensing tip 211 i mounted on the nozzle 71 i possible by performingthe suction and the discharge of gases with respect to the nozzle 71 i;and a punching mechanism 55 which is driven by the suction-dischargemechanism 53, for punching a film that covers the apertures of theliquid housing parts of the container group 20 to house various liquidsin advance.

The mount 30 further has: an on-mount measuring end transfer mechanism41 that moves a measuring end 44, and therefore the measuring device 40,along the Y axis direction, which is the longitudinal direction of themount 30; a plurality (twelve in this example) of coupling ends 31 ithat can be simultaneously directly or indirectly joined with theapertures of the reaction containers 231 i having light guide portions33 i that optically connect with the interior of the joined reactioncontainer 231 i; and a heater 37 as a heating portion that heats thecoupling ends 31 i for preventing condensation at the ends of thecoupling ends 31 i or on a mounted sealing lid 251 which hastransparency. Furthermore, the measuring device 40 has the measuring end44 to which is provided a light guide portion 43 optically connectableto the light guide portions 33 i which guide the movement of themeasuring device 40 on the mount 30 along the Y axis direction and areprovided on the coupling ends 31 i in the interior.

The container group 20 comprises a plurality (twelve in this example) ofexclusive regions 20 i that correspond to the respective nozzles, inwhich a single (a single group corresponds to a single nozzle in thisexample) nozzle enters and the other nozzles do not enter. The exclusiveregions 20 i have a liquid housing part groups 27 i which comprise aplurality of storage parts in which reagent solutions, and the like, arehoused or are able to be housed, a sealing lid storage part 25 i inwhich one or two or more sealing lids 251 which have transparency, andthat are detachably mounted on the coupling ends 31 i provided on themount 30, are housed or are able to be housed, and housing parts fortips and the like 21 i that house a plurality of dispensing tips 211 ithat are detachably mounted on the nozzle, samples, and the like. Theliquid housing part group 27 i at the very least has one or two or moreliquid housing parts that house a magnetic particle suspension, and twoor more liquid housing parts that house a solution for separating andextracting used for the separation and the extraction of nucleic acidsand the fragments thereof. Furthermore, if necessary, it additionallyhas two or more liquid housing parts that house an amplificationsolution used for the amplification of nucleic acids, and a liquidhousing part that houses a sealing liquid for sealing the amplificationsolution housed in the reaction container 231 i within the reactioncontainer 231 i.

It is preferable for the exclusive regions 20 i to displayidentification data that identifies the respective exclusive regions 20i.

The CPU+program 60 at the very least has a nucleic acid processingcontroller 63 that performs instructions for a series of processes suchas: the extraction and the amplification of nucleic acids and thefragments thereof, the sealing of the amplification solution, and thelike, with respect to the temperature controller 29, the nozzle headtransfer mechanism 51, the tip holding-detaching mechanism 59, thesuction-discharge mechanism 53, the magnetic force part 57, and thenozzle Z axis transfer mechanism 75; and a measurement control portion61 that, following control of the nozzle head transfer mechanism 51 andthe mount Z axis transfer mechanism 35 such that the coupling ends 31 iare simultaneously directly or indirectly joined with the apertures ofthe plurality (twelve in this example) of reaction containers 231 i,performs instructions for a measurement by the measuring device 40 bycontrolling the on-mount measuring end transfer mechanism 41 such thatthe light guide portions 33 i of the coupling ends 31 i and the lightguide portion 43 of the measuring end 44 are optically connected.

Furthermore, the nucleic acid processing controller 63 has an extractioncontrol part 65 and a sealing lid control part 67. The nucleic acidprocessing controller 63 has the extraction control part 65 thatperforms instructions for a series of processes for the extraction ofnucleic acids and the fragments thereof with respect to the tipholding-detaching mechanism 59, the suction-discharge mechanism 53, themagnetic force part 57, the nozzle Z axis transfer mechanism 75, thenozzle head transfer mechanism 51, and the mount Z axis transfermechanism 35, and the sealing lid control part 67 that performsinstructions for the sealing process by the sealing lid with respect tothe mount Z axis transfer mechanism 35 and the nozzle head transfermechanism 51.

Herein, a variety of more specific exemplary embodiments of theautomatic response/light measurement device 10 according to theembodiment of the present invention mentioned above are described withreference to FIG. 2 to FIG. 11. FIG. 2 is a perspective view of a firstexemplary embodiment of the present invention.

FIG. 2A is a drawing showing an external view of the automaticresponse/light measurement device 10, which has: an enclosure 11 with asize of 350 mm in depth (Y axis direction), 600 mm in width (X axisdirection) and 600 mm in height (Z axis direction), in which thecontainer group 20, the temperature controller 29, the nozzle head 50,the nozzle head transfer mechanism 51, and the CPU+program 60 are builtinto the interior; a control panel 13 provided on the enclosure 11having a liquid crystal display portion and operation keys; and a handle15 that, in addition to being used for opening and closing of the door17, forms a support member that horizontally supports the door 17 in acase where it is opened.

FIG. 2B is a drawing showing the door 17 opened, a guide rail 19provided on the rear side of the door 17, and a stage 22 that, in a casewhere the door 17 is opened and is horizontally placed, is guided by theguide rail 19 and is able to be pulled out onto the rear surface of thedoor 17.

FIG. 2C is a drawing showing the stage 22 pulled out onto the door 17,and the container group 20 is integrated into the stage 22. The nozzlehead 50 is provided on the interior of the enclosure 11. The housingparts for tips and the like 21 are integrated into the stage 22.

FIG. 3 is a plan view showing enlarged, the container group 20 shown inFIG. 2, which is integrated into the stage 22. The container group 20 isone in which twelve exclusive regions 20 i (i=1, . . . , 12), whereinthe longitudinal direction thereof is along the X axis direction andstorage parts are arranged in a single row form, are arranged inparallel along the Y axis direction at a pitch of 18 mm for example. Theexclusive regions 20 i have: a sealing lid storage part 25 i whichhouses a single sealing lid 251 i which has transparency, that isdetachably mounted on the twelve coupling ends 31 i provided on themeasurement mount 30; a reaction container 231 i; a reaction tubestorage cavity 241 i; a reaction container 242 i; 10 liquid housing partgroups 27 i; and housing parts for tips and the like 21 i that house asample and one or two or more dispensing tips 211 i.

The capacity of the reaction containers 231 i is of the order ofapproximately 200 μL, and the capacity of the other reaction containers,the liquid housing parts, and the tubes is of the order of approximately2 mL.

The reaction containers 231 i are used for the amplification of nucleicacids and the fragments thereof, and temperature control is performed bymeans of the temperature controller 29 based on a predeterminedamplification method, such as a thermal cycle (4° C. to 95° C.) forexample. The reaction container 231 i is formed with two levels as shownin FIG. 6A for example, and has a narrow-mouthed piping part 233 iprovided on the lower side in which the amplification solution 234 i ishoused, and a wide-mouthed piping part 232 i provided on the upper side,to which the sealing lid 251 i is fittable. The inner diameter of thewide-mouthed piping part 232 i is 8 mm for example. The inner diameterof aperture of the narrow-mouthed piping part 233 i is approximately 5mm for example. The reaction tube housed in the reaction tube storagecavity 241 i, and the reaction container 242 i are temperaturecontrolled for incubation in a constant temperature state of 55° C. forexample.

The solution for separating and extracting is housed in the liquidhousing part group 27 i as follows. There are 10 liquid housing parts intotal in which are respectively stored; 40 μL of Lysis 1 in a firstliquid housing part, 200 μL of Lysis 2 in a second liquid housing part,500 μL of a binding buffer solution in a third liquid housing part, amagnetic particle suspension in a fourth liquid housing part, 700 μL ofa washing liquid 1 in a fifth liquid housing part, 700 μL of a washingliquid 2 in a sixth liquid housing part, a dissociation liquid in aseventh liquid housing part, an eighth and a ninth liquid housing partthat are empty, and 1.2 mL of distilled water in a tenth liquid housingpart, and the reagents, and the like, are prepacked by the aperturesthereof being covered by a punchable film.

It is assumed that the housing parts for tips and the like 21 i retainsthree dispensing tips 211 i, a tube housing 200 μL of a sample, such asa suspension of bacteria, cells, and the like, or whole blood, and atube housing 1300 μL of isopropyl alcohol (i-Propanol) as a portion ofthe solution for separating and extracting proteins used for theremoval, and the like, of proteins.

FIG. 4 is a drawing showing the nozzle head 50 according to the firstexemplary embodiment of the present invention.

The nozzle head 50 has: a nozzle arrangement portion 70; a tipholding-detaching mechanism 59; a suction-discharge mechanism 53; apunching mechanism 55; a magnetic force part 57; a nozzle Z axistransfer mechanism 75; a measurement mount 30; a measuring device 40provided on the mount 30 having a measuring end 44; an on-mountmeasuring end transfer mechanism 41 that moves the measuring end 44 onthe mount 30; and a mount Z axis transfer mechanism 35.

The nozzle arrangement portion 70 is provided with a cylinder supportmember 73 that supports twelve cylinders 531 such that they are arrangedalong the Y axis direction at a predetermined pitch of 18 mm forexample. Furthermore, the downward ends of the cylinders 531 areprovided with the nozzles 71 i such that they are communicated with thecylinders 531.

The tip holding-detaching mechanism 59 has: a tip retaining member 591in which is provided twelve semicircular notch portions 592 forretaining on the nozzles 71 i the total of twelve dispensing tips 211 imounted on the nozzles 71 i, that extends in the Y axis direction and isformed in a comb shape such that it is axially supported on the cylindersupport member 73 via arms 596; and a tip detaching member 598 which isprovided with shafts for detaching 599 on both sides, that detaches thetwelve dispensing tips 211 i from the nozzles 71 i.

The suction-discharge mechanism 53 has: the cylinder 531 for performingsuction and discharge of gases with respect to the dispensing tips 211 iwhich are communicated with the nozzles 71 i and mounted on the nozzles71 i, and a piston rod 532 that slides within the cylinder 531; a driveplate 536 that drives the piston rod 532; a ball screw 533 that threadswith the drive plate 536; a nozzle Z axis movable body 535 that, inaddition to axially supporting the ball screw 533, is integrally formedwith the cylinder support member 73; and a motor 534 mounted on thenozzle Z axis movable body 535 that rotatingly drives the ball screw533.

The punching mechanism 55 is provided with punching pins 551 i atpositions corresponding to the arrangement of the nozzles 71 i, alongthe lower edge of a square shaped support frame 552 along a verticalsurface on a side opposing the side on which the cylinder 531 of thedrive plate 536 is provided. The ends of the pins 551 i are positionedabove the lower ends of the nozzles 71 at the time of suction anddischarge, and are not lowered past the lower ends of the nozzles 71 i.On the other hand, at the time of punching, although the ends of thepunching pins 551 i are lowered past the lower ends of the nozzles 71 idue to the drive plate 536 being lowered past the lower limit of thesuction and discharge range, the upper edge of the cylinder 531 is notreached. As a result of this lowering, the punching pins 551 i are ableto punch the film covering the apertures of the twelve liquid housingpart groups 27 i of the container group 20, which are arranged in asingle row form.

The magnetic force part 57 has a magnet 571 that is provided such thatit can approach and separate with respect to the narrow diameterportions 211 ia of the dispensing tips 211 i detachably mounted on thenozzles 71 i, and is able to apply and remove a magnetic field in theinterior of the dispensing tips 211 i.

The nozzle Z axis transfer mechanism 75 has: a ball screw 752 thatthreads with the Z axis movable body 535 and vertically moves the Z axismovable body 535 along the Z direction; a nozzle head substrate 753 thataxially supports the ball screw 752, and in addition to axiallysupporting the magnet 57 on the lower side thereof such that it ismovable in the X axis direction, is itself movable in the X axisdirection by means of the nozzle head transfer mechanism 51 mentionedbelow; and a motor 751 provided on the upper side of the nozzle headsubstrate 753 that rotatingly drives the ball screw 752.

The measurement mount 30 comprises a horizontal plate 30 a and avertical plate 30 b, which are letter-L shaped plates in cross-section,and is provided with twelve coupling ends 31 i having light guideportions 33 i, which are directly or indirectly joinable with theapertures of the reaction containers 231 i and are optically connectedwith the interior of the reaction containers 231 i, protruding in thedownward direction from the horizontal plate 30 a. Furthermore, thebases of the coupling ends 31 i are provided with a heater 37 that heatsthe sealing lids 251 mounted on the coupling ends 31 i and preventscondensation. The temperature of the heater 37 is set to approximately105° C. for example. Since the mount 30 is supported by the nozzle headsubstrate 753 via the nozzle head mount Z axis transfer mechanism 35such that it is movable in the Z axis direction, it is movable in thenozzle X axis direction and Z axis direction.

The mount Z axis transfer mechanism 35 has: a side plate 355 provided onthe nozzle head substrate 753; a mount driving band-shaped member 354that is supported by a timing belt 352 spanning between two sprockets353 arranged in the vertical direction axially supported by the sideplate 355, and vertically moves in the Z axis direction; and a motor 351attached to the rear side of the side plate 355 that rotatingly drivesthe sprockets 353.

A transfer groove 32 is etchingly provided on the horizontal plate 30 aof the mount 30 along the Y axis direction such that the upper ends ofthe light guide portions 33 i provided on the coupling ends 31 i arearranged at the bottom thereof. Furthermore, the measuring device 40 ismovably provided along the Y axis direction by means of the measuringend 44 of the measuring device 40 being inserted within the groove 32and sliding. The measuring device 40 is one that supports fluorescencemeasurements, and has: a light receiving portion 47 that receives thefluorescent light generated in the reaction containers 231 i; anirradiation portion 46 that irradiates the reaction containers 231 iwith an excitation light; and the measuring end 44. Moreover, themeasuring end 44 is provided with a light guide portion 43 that isoptically connectable to the light guide portions of the coupling ends31 i.

The vertical plate 30 b of the mount 30 is provided with the on-mountmeasuring end transfer mechanism 41. The on-mount measuring end transfermechanism 41 has: two sprockets 353 on the surface of the vertical plate30 b that are arranged along the Y axis direction; a timing belt 412spanning between the sprockets 413; a joined portion 415 that is joinedwith the timing belt 412 and is also joined with the measuring end 44 ofthe measuring device 40; a guide rail 414 that guides the Y axisdirection movement of the joined portion 415; and a motor thatrotatingly drives the sprockets 413.

FIG. 5 is a drawing showing, at the time the dispensing tips 211 i aremounted on the nozzles 71 i, the dispensing tips 211 i and the operationand the state in which the dispensing tips 211 i are retained on thenozzles 71 i using the tip holding-detaching mechanism 59. Thedispensing tips 211 i comprise a narrow diameter portion 211 ia, a thickdiameter portion that has a thicker diameter than the narrow diameterportion 211 ia, a mounting portion 211 ic that as a whole has thelargest outer diameter, a mouth portion 211 id at the end in which theinflow and the outflow of liquids is performed, and a mounting aperture211 ie into which the nozzle 71 i is inserted.

The tip retaining member 591 is provided with twelve semicircular notchportions 592 with an inner diameter smaller than the outer diameter ofthe mounting portions 211 ic of the dispensing tips 211 i mentionedbelow, but larger than the outer diameter of the thick diameter portions211 b. The arm 596 is rotatingly driven by a rotating shaft 597 thatrotates via a belt 601 by means of a roller 602 that is rotatinglydriven by a motor 595.

The tip detaching member 598 is interlocked with the lowering of two tipdetaching shafts 599 and detaches the dispensing tips 211 i from thenozzles 71 i. The tip detaching shaft 599 is elastically supported bythe cylinder support member 73 by means of a spring 600 wrapped aroundthe outer periphery such that it is biased in the upward direction, andthe upper end thereof is positioned above the upper end of the cylinder531 but below the lower limit position of the vertical movement range ofthe normal suction and discharge of a cylinder drive plate 536 mentionedbelow. The two tip detaching shafts 599 are pushed in the downwarddirection by means of the cylinder drive plate 536 exceeding thevertical movement range and being lowered near the upper end of thecylinder 531, thus lowering the tip detaching member 598. The tipdetaching member 598 has twelve holes having an inner diameter that islarger than the outer diameter of the nozzles 71 i but smaller than themounting portions 211 ic, which represents the largest outer diameter ofthe dispensing tips 211 i, arranged at the pitch mentioned above suchthat the nozzles 71 i pass therethrough.

In a case where the retention of the tips is performed by the tipholding-detaching mechanism 59, following movement of the nozzle head50, namely of the tip retaining member 591 of the tip holding-detachingmechanism 59 to a position in which it is separated from the nozzles 71i, and of the arm 596 to the section in which the dispensing tips 211 iare housed in a state in which it is rotatingly driven, the nozzles 71 iare lowered by means of the nozzle Z axis transfer mechanism 75 andmounted by being inserted into the apertures 211 ie. Thereafter, tipretention is performed by rotating the tip retaining member 591 of thetip holding-detaching mechanism 59, and the notch portions 592 makingcontact with, or approaching, the thick diameter portions 211 ib on thelower side of the mounting portions 211 ic of the dispensing tips 211 i.At that time, by means of a support shaft 593, which protrudes on bothsides of the tip retaining member 591 and is inserted into long holes594 piercingly provided such that the longitudinal direction thereof issomewhat inclined with respect to the radius of rotation direction ofthe arm 596, moving within the long holes 594 in the rotation axisdirection, the notch portions 592 become positioned at positionsdirectly below the mounting portions 211 ic.

On the other hand, to detach the dispensing tips 211 i mounted on thenozzles 71 i, after rotating the tip retaining member 591 and separatingit from the dispensing tips 211 i, a detaching member 598 is lowered asa result of moving the detaching shaft 599 in the downward direction bylowering the drive plate 536 below the normal suction and dischargeposition, and the dispensing tips 211 i become detached from the nozzles71 i.

FIG. 6A is a drawing showing an example wherein a coupling end 31 iprovided on the mount 30, being a coupling end 31 i in which a sealinglid 251 i which has transparency is mounted on the coupling end 31 i, ismounted on the aperture of the reaction container 231 i of the exclusiveregion 20 i. The reaction container 231 i comprises a wide-mouthedpiping part 232 i, and a narrow-mouthed piping part 233 i communicatedwith the wide-mouthed piping part 232 i, that is formed narrower thanthe wide-mouthed piping part 232 i. The narrow-mouthed piping part 233 iis dried beforehand, or houses a liquid form amplification solution 234i. The wide-mouthed piping part 232 i and the narrow-mouthed piping part233 i are integrally joined with the base portion 230 of the container.Here, for the reagent for real-time amplification, 70 μL of a master mix(SYBR (registered trademark) Green Mix) consisting of enzymes, buffers,primers, and the like, is housed beforehand.

The aperture of the wide-mouthed piping part 232 i has a size into whichthe end of the sealing lid 251 i which has transparency, is fittable.Further, the coupling end 31 i has a size in which it is fittable withinthe sealing lid 251 i. At the time of fitting, it is preferable for thediameter of the light guide portion 33 i, which passes the interior ofthe coupling end 31 i, to be the same as the size of the diameter of theaperture of the narrow-mouthed piping part 233 i or larger.Consequently, it becomes possible to receive the light from the reactioncontainer 231 i with certainty. The narrow-mouthed piping part 233 i ishoused within a temperature control block 291 i that is heated or cooledby a temperature controller 29.

FIG. 6B is a drawing showing a state in which the coupling end 31 i,which protrudes from the horizontal plate 30 a of the mount 30 to thelower side, is joined with the reaction container 231 i in a state inwhich it is fitted to the sealing lid 251. FIG. 6C and FIG. 6D aredrawings showing an operation in which the measuring device 40 moves onthe mount 30. This operation is one in which, while moving along thegroove 32 by means of the on-mount measuring end transfer mechanism 41in a state in which the measuring end 44 is inserted into the groove 32,the light guide portions 33 i of the twelve coupling ends 31 i arrangedin the groove 32 and the light guide portion 43 of the measuring end 44are successively optically connected. The speed of the measuring end 44,and therefore the measuring device 40, on the measurement mount 30 isdetermined by considering the stable light receivable time, the numberof reaction containers, the pitch, and the like, and is controlled suchthat it becomes 100 mm to 500 mm per second in the case of a real-timePCR measurement for example. In the present exemplary embodiment, sincethe measuring end 44 moves by sliding within the groove 32, opticalnoise incident to the lower end surface of the measuring end 44 can beprevented.

FIG. 7 is a perspective view showing an automatic response/lightmeasurement device 100 according to a second exemplary embodiment.

The device 100 comprises a section corresponding to the automaticresponse/light measurement device 10 according to the first exemplaryembodiment, which has the nozzle head 50, the nozzle head transfermechanism 51, and the container group 20 built into the stage 22, and afeeding device for samples and the like 80.

Here, the nozzle head transfer mechanism 51 is a mechanism that has atiming belt 511 and a joined portion 512 that joins to it, and makes thenozzle head 50 movable in the X axis direction, and is the same as inthe automatic response/light measurement device 10 according to thefirst exemplary embodiment.

On the other hand, the feeding device for samples and the like 80 is adevice for supplying parent samples, and the like, with respect to thecontainer group 20 by dispensing, and the stage 22, to which thecontainer group 20 supplied with the parent samples and the like, isbuilt-in, becomes automatically moved to the automatic response/lightmeasurement device. It has: a parent container group 81 which houses theparent samples and the like; a nozzle head 89 having a tip detachingmechanism, a suction-discharge mechanism, and a single nozzle 85 that,in addition to the suction and discharge of gases being performed bymeans of the mechanisms, has a dispensing tip 211 i detachably mounted,that has a mechanism that moves along the Z axis direction with respectto the parent container group 81 and the housing parts for tips and thelike 21 of the container group 20; an X axis movable body 87 having a Yaxis transfer mechanism that moves the nozzle head 89 in the Y axisdirection with respect to the parent container group 81 and the like; anX axis transfer mechanism 86 that moves the X axis movable body 87 alongthe X axis direction with respect to the parent container group 81 andthe like; and the parent container group 81. The parent container group81 has: a parent sample storage part group 82 arranged in a 12 row x 8column matrix form that houses the parent samples to be supplied to thehousing parts for tips and the like 21 of the container group 20; adistilled water/washing liquid group 83; and a reagent bottle group 84.Reference symbol 88 represents a seat portion of the device 100.

The feeding device for samples and the like 80 moves the nozzle head 89to a storage part of the container group 20 housing a dispensing tip 211i, then by lowering mounts the dispensing tip 211 i on the nozzle 85thereof, and by using the Z axis transfer function of the nozzle head89, the X axis transfer mechanism 86, and the Y axis transfer functionof the X axis movable body 87, moves to the corresponding parent samplestorage part of the parent sample storage part group 82, aspirates thesample, and transfers it to the corresponding storage part of thehousing parts for tips and the like 21 i of the container group 20. Thedispensing tip 211 i, in which the transfer is completed, is detachedinto the storage part by the tip detaching portion. The necessarywashing liquids, reagents, and the like, become supplied to the housingparts for tips and the like 21 i by the same method using otherdispensing tips 211 i.

FIG. 8 is a drawing showing the interior of the seat portion 88, inwhich a plurality of stages 22 are layered on the lower side of thefeeding device for samples and the like 80. Furthermore, when the samplefeeding process is completed with respect to the stage 22 of theuppermost level, and the stage 22 moves along the Y axis direction andis positioned on the lower side of the automatic response/lightmeasurement device 10, since the stages 22 on the lower side are biasedby an elastic force and the like, they successively become moved to theupper level side. Consequently, rapid and efficient processing can beperformed.

FIG. 9 is a drawing showing a measuring device 401 according to a thirdexemplary embodiment of the present invention.

The measuring device 401 is one in which a plurality (six in thisexample) of specific wavelength measuring devices 401 j (j=1, 2, 3, 4,5, 6) are, including the measuring ends 441, integrally joined inparallel and in a single row form. Reference symbol 45 represents ashaft that serves as a measuring end bundling portion for integrallybundling together the specific wavelength measuring devices 401 j. Thisshaft is one that penetrates the holes piercingly provided in thespecific wavelength measuring devices 401 j, which have an innerdiameter that is somewhat larger than the outer diameter of the shaft,and joins these by tightening screw type end portions having asufficiently larger outer diameter than the holes.

The pitch of the specific wavelength measuring devices 401 j in themovement direction, assuming a pitch between the reaction containers 231i of the container group 20 or the end portions of the light guideportions 33 i of the coupling ends 31 i on the mount 30 of 18 mm, is 9mm, which is half thereof. Therefore, the on-mount measuring endtransfer mechanism 41 moves the measuring ends 441 j of the specificwavelength measuring devices 401 j intermittently such that theymomentarily stop at each pitch advance, or continuously.

FIG. 9C is a drawing showing the interior of the specific wavelengthmeasuring device 401 j. The measuring device 401 j has: a measuring end441 in which a lens 444, wherein excitation light exits to the reactioncontainer 231 i and fluorescent light from the reaction containers 231 iis incident, and a dichroic mirror 445 are provided to a light guideportion; an irradiation portion 461 having a filter 466, a lens 465, andan LED 464 for irradiating excitation light; and a light receivingportion 471 having a filter 476, a lens 475 and a photodiode 474.

According to the third exemplary embodiment of the present invention,the light from the LED 464 is such that the excitation light of aspecific wavelength band that passes the filter 466 is reflected by thedichroic mirror 445 and is irradiated through the lens 444 of themeasuring end 441 and into the reaction containers 231 i, and thefluorescent light excited by the excitation light passes the lens 444 ofthe measuring end 441, is transmitted through the dichroic mirror 445,and the fluorescent light of a predetermined specific wavelengthselected by the filter 476 passes the lens 475, and is incident to thephotodiode 474 and is received. The fluorescent light of otherwavelengths is also successively received using the six specificwavelength measuring devices 403 j.

FIG. 10 is a drawing showing a measuring device 402 according to afourth exemplary embodiment of the present invention.

The measuring device 402 is one in which a plurality (six in thisexample) of specific wavelength measuring devices 402 j are, includingthe measuring ends 442, integrally joined in parallel and in a singlerow form. The specific wavelength measuring devices 402 j differ fromthe specific wavelength measuring devices 401 j according to the thirdexemplary embodiment mentioned above with regard to the interiorthereof, as shown in FIG. 10C.

The specific wavelength measuring device 402 j according to the presentexemplary embodiment has: a measuring end 442 that, in addition tohaving an optical fiber 469 for the excitation light to exit to thereaction container 231 i and an optical fiber 479 for the light from thereaction container 231 i to be incident, is provided with an irradiationend 446 of the optical fiber 469 and a light receiving end 447 of theoptical fiber 479 on the lower end; an LED 467 that irradiatesexcitation light through the optical fiber 469; an irradiation portion462 having a filter 468; and a light receiving portion 472 having theoptical fiber 479, a drum lens 478, a filter 477 and a photodiode 474.

FIG. 11 is a drawing showing a measuring device 403 according to a fifthexemplary embodiment of the present invention.

The measuring device 403 is one in which each of the exclusive regions20 i has four reaction containers 235 i, 236 i, 237 i, and 238 i, andthe reaction container groups 23 i comprise in the X axis direction withrespect to the movement direction (Y axis direction) of the measuringdevice 403, two rows comprising the reaction container row 235 i, 237 iand the reaction container row 236 i, 238 i at a spacing of 9 mm pitchfor example.

The measuring device 403 is one in which a plurality (six in thisexample) of specific wavelength measuring devices 403 j are, includingthe measuring ends 443, integrally joined in parallel and in a singlerow form. The specific wavelength measuring devices 403 j differ fromthe measuring devices 401 j and 402 j mentioned above with regard to theinterior thereof, as shown in FIG. 11C.

FIG. 11C is a drawing showing the interior of the measuring device 403 jaccording to the present exemplary embodiment. The measuring device 403j has: a measuring end 443 i having a lens 444, wherein excitation lightexits to the reaction container 235 i or the reaction container 237 iand fluorescent light from the reaction container 235 i or the reactioncontainer 237 i is incident, and a lens 448, wherein excitation lightexits to the reaction container 236 i or the reaction container 238 iand fluorescent light from the reaction container 236 i or the reactioncontainer 238 i is incident, a dichroic mirror 445, and a rotatablerhombic prism 449 for switching to either a light guide portion thatconnects the dichroic mirror 445 and the lens 444 or a light guideportion that connects the lens 448 and the dichroic mirror 445; anirradiation portion 463 having a filter 466, a lens 465, and an LED 464for irradiating excitation light; and a light receiving portion 473having a filter 476, a lens 475, and a photodiode 474.

The position of the rhombic prism 449 in FIG. 11C represents a casewhere the incidence and exiting of the light is performed with respectto the reaction containers 235 i or 237 i via the lens 444. Furthermore,the position of the rhombic prism 449 in FIG. 11D represents a casewhere the incidence and exiting of the light is performed with respectto the reaction container 236 i or the reaction container 238 i via thelens 448.

The speed of the measuring ends 441, 442, and 443, and therefore themeasuring devices 401, 402, and 403 with respect to the container group20 or the measurement mount 30 is approximately 100 mm to 500 mm forexample.

Next, a series of processing operations that perform real-time PCR ofthe nucleic acids of a sample containing bacteria using the automaticresponse/light measurement device 10 according to the first exemplaryembodiment is described. Step S1 to step S13 below correspond toseparation and extraction processing.

In step S1, the door 17 of the automatic response/light measurementdevice 10 shown in FIG. 2 is opened, the stage 22 is pulled out, and byutilizing the feeding device for samples and the like 80 for example,which is separately provided from the container group 20 and on thestage 22, the samples, which are subject to testing, various washingliquids, and various reagents, are supplied beforehand, and furthermore,a liquid housing part in which the reagents and the like are prepackedis mounted.

In step S2, following returning of the stage 22 and closing of the door17, the start of the separation and extraction and amplificationprocessing is instructed by means of the operation of the touch panel ofthe control panel 13 for example.

In step S3, the extraction control part 65 provided to the nucleic acidprocessing controller 63 of the CPU+program 60 of the automaticresponse/light measurement device 10 instructs the nozzle head transfermechanism 51 and moves the nozzle head 50 in the X axis direction,positions the punching pin 551 i above the first liquid housing part ofthe liquid housing part group 27 i of the container group, and punchesthe film covering the aperture of the liquid housing part by loweringthe drive plate 536 of the suction-discharge mechanism 53 past the lowerlimit of the suction and discharge range, and in the same manner, theother liquid housing parts of the liquid housing part group 27 i and thereaction container group 23 i are successively punched by moving thenozzle head 50 in the X axis direction and using the suction-dischargemechanism 53.

In step S4, the nozzle head 50 is again moved in the X axis directionand moved to the housing parts for tips and the like 21 i, and thenozzles 71 i are lowered by means of the nozzle Z axis transfermechanism 75, and the dispensing tips 211 i are mounted. Next, bybringing the tip retaining member 591 of the tip holding-detachingmechanism 59 with the thick diameter portions 211 ib of the dispensingtips 211 i, the dispensing tips 211 i are retained on the nozzles 71 iand detachment is prevented. Following raising by the nozzle Z axistransfer mechanism 75, the dispensing tip 211 i is moved along the Xaxis by means of the nozzle head transfer mechanism 51, and after itreaches the tenth liquid housing part of the liquid housing part group27 i, it is loweringly inserted into the narrow diameter portion 211 iaof the dispensing tip 211 i by the nozzle Z axis transfer mechanism 75.Then, 50 ∥L of distilled water is aspirated by means of thesuction-discharge mechanism 53, and following raising of the dispensingtip 211 i above the liquid housing part again, the dispensing tip 211 iis moved by the nozzle head transfer mechanism 51, and the distilledwater is discharged within the eighth liquid housing part and housed asa dissociation liquid. In the same manner, 350 μL of distilled water ishoused in the sixth liquid housing part.

In step S5, furthermore to the solution components (NaCl, SDS solutions)housed beforehand in the third liquid housing part and the fifth liquidhousing part, and to the distilled water housed in the sixth liquidhousing part, as mentioned above, a predetermined amount of isopropylalcohol (i-Propanol) is aspirated from the tube, and predeterminedamounts are respectively dispensed to the third liquid housing part, thefifth liquid housing part, and the sixth liquid housing part. By sodoing, 500 μL of a binding buffer solution (NaCl, SDS, i-Propanol), 700μL of a washing liquid 1 (NaCl, SDS, i-Propanol), and 700 μL of awashing liquid 2 (water 50%, i-Propanol 50%) are respectively preparedas solutions for separating and extracting within the third, the fifth,and the sixth liquid housing parts.

In step S6, following movement to, among the housing parts for tips andthe like 21 i, the sample tube in which the sample is housed, the narrowdiameter portion 211 ia of the dispensing tip 211 i is loweringlyinserted using the nozzle Z axis transfer mechanism 75, and, withrespect to the suspension of the sample housed in the sample tube,following suspension of the sample within the liquid by repeating thesuction and the discharge by raising and lowering the drive plate 536 ofthe suction-discharge mechanism 53, the sample suspension is aspiratedwithin the dispensing tip 211 i. The sample suspension is moved alongthe X axis by means of the nozzle head transfer mechanism 51 to thefirst liquid housing part of the liquid housing part group 27 i housingthe Lysis 1 (enzyme) representing the solution for separating andextracting, and the narrow diameter portion 211 ia of the dispensing tip211 i is inserted through the hole in the punched film, and the suctionand the discharge is repeated in order to stir the sample suspension andthe Lysis 1.

In step S7, the entire amount of the stirred liquid is aspirated by thedispensing tip 211 i, and incubation is performed by housing it in thereaction tube retained in the storage cavity 241 i that is set to 55° C.by means of the constant temperature controller. Consequently, theprotein contained in the sample is broken down and made a low molecularweight. After a predetermined time has elapsed, the reaction mixture isleft in the reaction tube, the dispensing tip 211 i is moved to thesecond liquid housing part of the liquid housing part group 27 i bymeans of the nozzle head transfer mechanism 51, and the entire amount ofthe liquid housed within the second liquid housing part is aspirated byusing the nozzle Z axis transfer mechanism 75 and the suction-dischargemechanism 53, and it is transferred using the dispensing tip 211 i bymeans of the nozzle head transfer mechanism 51, and the reactionsolution is discharged within the third liquid housing part bypenetrating the hole in the film and inserting the narrow diameterportion.

In step S8, the binding buffer solution housed within the third liquidhousing part, which represents a separation and extraction solution, andthe reaction solution are stirred, the solubilized protein is furtherdehydrated, and the nucleic acids or the fragments thereof are dispersedwithin the solution.

In step S9, using the dispensing tip 211 i, the narrow diameter portionthereof is inserted into the third liquid housing part by passingthrough the hole in the film, the entire amount is aspirated and thedispensing tip 211 i is raised by means of the nozzle Z axis transfermechanism 75, and the reaction solution is transferred to the fourthliquid housing part, and the magnetic particle suspension housed withinthe fourth liquid housing part is stirred with the reaction solution. Acation structure in which Na+ ions bind to the hydroxyl groups formed onthe surface of the magnetic particles contained within the magneticparticle suspension is formed. Consequently, the negatively charged DNAis captured by the magnetic particles.

In step S10, the magnetic particles are adsorbed on the inner wall ofthe narrow diameter portion 211 ia of the dispensing tip 211 i byapproaching the magnet 571 of the magnetic force part 57 to the narrowdiameter portion 211 ia of the dispensing tip 211 i. In a state in whichthe magnetic particles are adsorbed on the inner wall of the narrowdiameter portion 211 ia of the dispensing tip 211 i, the dispensing tip211 i is raised by means of the nozzle Z axis transfer mechanism 75 andmoved from the fourth liquid housing part to the fifth liquid housingpart using the nozzle head transfer mechanism 51, and the narrowdiameter portion 211 ia is inserted by passing through the hole in thefilm.

In a state in which the magnetic force within the narrow diameterportion 211 ia is removed by separating the magnet 571 of the magneticforce part 57 from the narrow diameter portion 211 ia of the dispensingtip 211 i, as a result of repeating the suction and the discharge of thewashing liquid 1 (NaCl, SDS, i-Propanol) housed in the fifth liquidhousing part, the magnetic particles are released from the inner wall,and the protein is washed by stirring within the washing liquid 1.Thereafter, in a state in which the magnetic particles are adsorbed onthe inner wall of the narrow diameter portion 211 ia as a result ofapproaching the magnet 571 of the magnetic force part 57 to the narrowdiameter portion 211 ia of the narrow diameter portion 211 ia again, thedispensing tip 211 i is, by means of the nozzle Z axis transfermechanism 75, moved from the fifth liquid housing part to the sixthliquid housing part by means of the nozzle head transfer mechanism 51.

In step S11, the narrow diameter portion 211 ia of the dispensing tip211 i is inserted by passing through the hole in the film using thenozzle Z axis transfer mechanism 75. By repeating the suction and thedischarge of the washing liquid 2 (i-Propanol) housed in the sixthliquid housing part in a state in which the magnetic force within thenarrow diameter portion 211 ia is removed by separating the magnet 571of the magnetic force part 57 from the narrow diameter portion 211 ia ofthe dispensing tip 211 i, the magnetic particles are stirred within theliquid, the NaCl and the SDS is removed, and the protein is washed.Thereafter, in a state in which the magnetic particles are adsorbed onthe inner wall of the narrow diameter portion 211 ia by approaching themagnet 571 of the magnetic force part 57 to the narrow diameter portion211 ia of the dispensing tip 211 i again, the dispensing tip 211 i is,following raising by means of the nozzle Z axis transfer mechanism 75,moved from the sixth liquid housing part to the ninth liquid housingpart, in which the distilled water is housed, by means of the nozzlehead transfer mechanism 51.

In step S12, by means of the nozzle Z axis transfer mechanism 75, thenarrow diameter portion 211 ia of the dispensing tip 211 i is loweredthrough the hole, and by repeating the suction and the discharge of thewater at a slow flow rate in a state in which the magnetic force isapplied within the narrow diameter portion 211 ia of the dispensing tip211 i, the i-Propanol is substituted by water and is removed.

In step S13, by means of the nozzle head transfer mechanism 51, thedispensing tip 211 i is moved along the X axis direction and the narrowdiameter portion 211 ia is inserted into the eighth liquid housing partthrough the hole in the film. By stirring the magnetic particles byrepeating the suction and the discharge within the distilled water,which represents the dissociation liquid, in a state in which the magnet571 of the magnetic force part 57 is separated from the narrow diameterportion 211 ia of the dispensing tip 211 i and the magnetic force isremoved, the nucleic acids or the fragments thereof retained by themagnetic particles are dissociated (eluted) from the magnetic particlesinto the liquid. Thereafter, a magnetic field is applied within thenarrow diameter portion and the magnetic particles are adsorbed on theinner wall by approaching the magnet 571 to the narrow diameter portion211 ia of the dispensing tip 211 i, and the solution containing theextracted nucleic acids, and the like, is made to remain in the eighthliquid housing part. The dispensing tip 211 i is moved to the storagepart of the housing parts for tips and the like 21 i in which thedispensing tip 211 i was housed, by means of the nozzle head transfermechanism 51, and following separation of the tip retaining member 591of the tip holding-detaching mechanism 59 from the dispensing tip 211 i,the dispensing tip 211 i to which magnetic particles are adsorbed, isdetached from the nozzle 181 together with the magnetic particles anddropped into the storage part, using the detaching member 598.

The following step S14 to step S17 corresponds to nucleic acidamplification and measurement processing.

In step S14, the nozzle head 50 is moved by means of the nozzle headtransfer mechanism 51, and the coupling end 31 i of the measurementmount 30 is moved above the sealing lid storage part 25 i housing thesealing lids 251 of the container group 20. The sealing lid 251 ismounted by fitting to the lower end of the coupling end 31 i by beinglowered using the mount Z axis transfer mechanism 35. After being raisedby the mount Z axis transfer mechanism 35, the coupling end 21 i mountedwith the sealing lid 251 is positioned on the reaction container 231 iusing the nozzle head transfer mechanism 51, and by lowering thecoupling end 31 i mounted with the sealing lid 251 by means of the mountZ axis transfer mechanism 35, the sealing lid 251 and also the apertureof the wide-mouthed piping part 232 i of the reaction container 231 iare joined.

In step S15, due to an instruction by the nucleic acid processingcontroller 63, the temperature controller 29 instructs a temperaturecontrol cycle by real-time PCR, such as a cycle in which the reactioncontainer 231 i is heated for five seconds at 96° C. and heated for 15seconds at 60° C., to be repeated forty nine times for example.

In step S16, when temperature control at each cycle is started by thenucleic acid processing controller 63, the measurement control portion61 determines the start of elongation reaction processing at each cycle,and instructs the continuous or intermittent movement of the measuringend 44, and therefore the measuring device 40. For the movement speedthereof, it is moved at a speed that is calculated based on the stablelight receivable time and the number (twelve in this example) ofexclusive regions 20 i. Consequently, the receiving of light from alltwelve reaction containers 231 i within the stable light receivable timebecomes completed.

In step S17, the measurement control portion 61 determines the moment ofeach optical connection between the light guide portions 33 i of thecoupling ends 31 i and the light guide portion 43 of the measuring end44, and instructs the irradiation and the receiving of excitation lightto the measuring device 40.

This measurement is executed with respect to cycles in which exponentialamplification is performed, and an amplification curve is obtained basedon the measurement, and various analyses are performed based on theamplification curve. At the time of the measurement, the measurementcontrol portion 61 heats the heater 37 and prevents the condensation onthe sealing lid 251, and a clear measurement can be performed. In a casewhere measurements are performed with respect to a plurality of types oftarget nucleic acids by real-time PCR, the measurement can be performedby executing using the measuring devices 401, 402, and 403 described inthe third, the fourth, and the fifth exemplary embodiments in place ofthe measuring device 40.

FIG. 12 is a block-diagram showing an automatic response/lightmeasurement device 110 according to a second embodiment of the presentinvention.

Elements that are the same as the automatic response/light measurementdevice 10 of the first embodiment are represented by the same referencesymbols, and the descriptions thereof are omitted.

The automatic response/light measurement device 110 according to thesecond embodiment differs from the automatic response/light measurementdevice 10 of the first embodiment in the respect that the nozzle head150 thereof has a measurement mount 130 that is different from themeasurement mount 30. Although the measurement mount 130 has a plurality(twelve in this example) of coupling ends 131 i having light guideportions 33 i, which are simultaneously directly or indirectly joinableto the apertures of the reaction containers 231 i and optically connectwith the interior of the joined reaction containers 231 i, it differsfrom the measurement mount 30 in the respect that the heat source of theheater 137, which represents a heating portion for heating the couplingends 131 i, is not provided to the coupling ends 131 i provided to themeasurement mount 130, or in the vicinity thereof.

The heat source of the heater 137 is provided to the container group 120or the stage. The container group 120 is one in which twelve exclusiveregions 120 i (i=1, . . . , 12), wherein the longitudinal directionthereof is along the X axis direction and storage parts are arranged ina single row form, are arranged in the Y axis direction for example.Each exclusive region 120 i has: a reaction container group 123 i; aliquid housing part group 27 i; a sealing lid storage part 25 i thathouses a single sealing lid 251 i which has transparency, that isdetachably mounted on the twelve coupling ends 131 i provided to themeasurement mount 130; and housing parts for tips and the like 21 i.

The reaction containers 123 i, the temperature controller 29, and theheater 137 are included in a reaction container control system 90.

FIG. 13 is a drawing showing a side view of the nozzle head 150. Thenozzle head 150 is different from the nozzle head 50 according to thefirst embodiment in that the heater 137 is not provided to themeasurement mount 130, and a heat source of the heater 137 is notprovided to the coupling ends 131 i.

FIG. 14A is a drawing showing a reaction container control system 901according to a first exemplary embodiment of the second embodiment, anda state in which the coupling end 131 i of the measurement mount 130 ismounted on an aperture of the reaction container group which is providedwith the plurality (twelve in this example) of reaction containers 231 iof the reaction container control system 901, and optical fibers 469 and479 of a specific wavelength measuring device 404 j for measuring lightof a predetermined wavelength or wavelength band, which moves on ahorizontal plate 130 a of the measurement mount 130 while beingsupported by a vertical plate 130 b, are connected to the coupling end131 i.

As shown in FIG. 14A, the reaction container control system 901 has: areaction container 231 i that houses target solutions of DNA possessinga target base sequence and the like, and in which reactions such asamplification are performed; a temperature control block 294 i of thetemperature controller 29, which corresponds to the heat source and thetemperature source of the heater 137 i; and a heat insulating plate 295i provided between a container base plate, which has a heat insulatingproperty, mounted with the plurality (twelve in this example) ofreaction containers 231 i, and the temperature control block 294 irepresenting the heat source and the temperature source of the heater137 i.

The reaction container 231 i comprises a wide-mouthed piping part 232 iand a narrow-mouthed piping part 233 i provided on the lower side of thewide-mouthed piping part 232 i that is communicated with thewide-mouthed piping part 232 i and formed narrower than the wide-mouthedpiping part 232 i, wherein the sealing lid 252 i which has transparency,is fitted and mounted on the wide-mouthed piping part 232 i, and thecoupling end 131 i representing the member for light measurement ismounted on the sealing lid 252 i.

The narrow-mouthed piping part 233 i has: a lower side wall section 233ai provided such that the temperature control block 294 is makingcontact; and a band-shaped upper side wall section 233 bi positioned onthe upper side leaving a spacing and, with the lower side wall section233 ai, sandwiching the heat insulating plate 295 i, that is adjacentlyprovided with the heat source of the heater 137 i.

According to the present exemplary embodiment, by means of theinstructions of the measurement control portion 161 (CPU+program 160),by controlling the heater 137 i according to the temperature control bythe temperature controller 29 such that, in the case of PCR, the upperside wall section 233 bi is heated at a fixed temperature (100° C. forexample) that is several degrees, or preferably approximately 5° C.,higher than the maximum predetermined temperature (94° C. for example),the sealing lid 252 i fitted to the wide-mouthed piping part 232 i ofthe reaction container 231 i is heated and condensation on the sealinglid can be prevented. At that time, the upper side wall section 233 biis separated by a predetermined spacing from the lower side wall section233 ai, in which the temperature control is performed, and the heatsource is made to make contact with, or approach, and heat the upperside wall section 233 bi, which has a smaller surface area than thelower side wall section. Therefore, the effect of heating on the upperside wall section 233 bi is that the sealing lid 252 i provided at aposition in the vicinity of the upper side wall section 233 bi isheated, and the lower end surface of the sealing lid 252 i is heated,and condensation can be prevented.

On the other hand, since the coupling end 131 i is on the upper side ofthe sealing lid 252 i, there is not nearly the effect of heating as forthe sealing lid 252 i. In the same manner, the lower side wall section233 ai becomes temperature controlled at the predetermined temperatureusing a Peltier element having a cooling function.

FIG. 14B is a cross-sectional view showing a reaction container controlsystem 902 according to a second exemplary embodiment of the automaticresponse/light measurement device 110 according to the secondembodiment.

The reaction container control system 902 is one in which a rod lens 430is provided to the light guide portion 33 i of the coupling end 132 i asan example of an optical system element. Consequently, the optical statefrom the reaction container 231 i is captured with certainty, andexcitation light can be uniformly irradiated into the reactioncontainer.

Since the present exemplary embodiment is one in which the heater 137 idoes not directly heat the coupling end 132 i and heats the sealing lid252 i by heating the upper side wall section of the reaction container231 i, the effect of heating does not readily reach the coupling end 132i, and even if optical elements such as the rod lens 430 is built intothe interior, the degradation or change in properties thereof, forexample, is prevented, and measurements with a high reliability can beperformed.

The foregoing embodiments have been specifically described in order tobetter understand the present invention, and they are in no way limitingof other embodiments. Therefore, modifications are possible within ascope that does not depart from the gist of the invention. Theconfigurations, shapes, materials, arrangements, and amounts of thenozzles, the dispensing tips, the punching pin, the container group, theexclusive regions thereof, the storage parts, the measuring end, themeasuring devices, the specific wavelength measuring devices, thesuction-discharge mechanism, the transfer mechanism, the magnetic forcepart, the heating portion, the reaction container, the sealing lid, themeasurement mount, the coupling end, the light guide portion, the nozzlehead, the temperature controller, the heater, and the like, and theutilized reagents and samples are also in no way limited by the examplesillustrated in the exemplary embodiments. Furthermore, although thenozzles were made to move with respect to the stage, it is possible toalso move the stage with respect to the nozzles.

Furthermore, in the foregoing descriptions, although the amplificationsolution was sealed using a sealing lid for the sealing of the reactioncontainer for PCR, it may be made such that, in its place or incombination, it is sealed using a sealing liquid, such as mineral oil.Moreover, in place of the punching pin, it is possible to performpunching by mounting a tip for punching on the nozzle. Although theplurality of specific wavelength measuring devices were joined by screwfastening both ends of a shaft that penetrates them, it is in no waylimited to this, and they may also be joined by storing the plurality ofspecific wavelength measuring devices within a frame for example.Furthermore, the joining is in no way limited to an integrated case, andit is possible for the plurality of specific wavelength measuringdevices or the measuring ends to be joined using a chain or in a chainform. Moreover, in the foregoing descriptions, although a real-time PCRmeasurement was described, it is in no way limited to this measurement,and it may also be applied to a variety of other measurements in whichtemperature control is performed. In the foregoing descriptions,although a case where the measuring device is provided to a dispensingdevice was described, it is not necessarily limited to this. Although acase where a measurement mount is used was described, it is alsopossible to not use a measurement mount and to directly and successivelyoptically connect the reaction container and the light guide portions ofthe measuring ends of the plurality of specific wavelength measuringdevices.

Furthermore, the devices described in the respective exemplaryembodiments of the present invention, the components that form thesedevices, or the components that form these components, can beappropriately selected, and can be mutually combined by applyingappropriate modifications. The spatial representations within thepresent application, such as “above”, “below”, “upper side”, “lowerside”, “interior”, “exterior”, “X axis”, “Y axis”, and “Z axis” are forillustration only, and are in no way limiting of the specific spatialdirections or arrangements of the construction.

INDUSTRIAL APPLICABILITY

The present invention is related to fields in which the processing,testing, and analysis of nucleic acids, which primarily includes DNA,RNA, mRNA, rRNA, and tRNA for example, is required, and is related toindustrial fields, agricultural fields such as food, agriculturalproducts, and fishery processing, chemical fields, pharmaceuticalfields, health care fields such as hygiene, insurance, diseases, andgenetics, and scientific fields such as biochemistry or biology forexample. The present invention is, in particular, able to be used inprocessing and analysis that handles various nucleic acids, and thelike, such as PCR and real-time PCR.

BRIEF DESCRIPTION OF THE REFERENCE SIGNALS

-   10, 100, 110 Automatic response/light measurement device-   20, 120 Container group-   20 i, 120 i (i=1, . . . , 12) Exclusive regions-   211 i (i=1, . . . , 12) Dispensing tips-   231 i (i=1, . . . , 12) Reaction containers-   30, 130 Measurement mount-   31 i, 131 i, 132 i (i=1, . . . , 12) Coupling ends-   37, 137 Heater (heating portion)-   40, 401 j, 402 j, 403 j, 404 j (j=1, . . . , 6) (Specific    wavelength) Measuring devices-   44, 441, 442, 443 Measuring end-   50, 150 Nozzle head-   53 Suction-discharge mechanism-   59 Tip holding-detaching mechanism-   61, 161 Measurement control portion-   70 Nozzle arrangement portion-   71 i (i=1, . . . , 12) Nozzles

1. An automatic response/light measurement device comprising: acontainer group in which two or more reaction containers are arranged; ameasurement mount provided with two or more coupling ends that aredirectly or indirectly joinable with apertures of said reactioncontainers, and have light guide portions that optically connect withthe interior of the joined reaction containers; a mount transfermechanism that makes said mount relatively movable with respect to saidcontainer group; a measuring device provided on said mount and having ameasuring end having at least one light guide portion that is opticallyconnectable to said light guide portions of said coupling ends, that isable to receive light based on an optical state within said reactioncontainers via said measuring end; an on-mount measuring end transfermechanism that makes said measuring end movable on said mount along themovement path passed by the two or more coupling ends; and a measurementcontrol portion that, following control of said mount transfer mechanismsuch that said coupling ends are simultaneously directly or indirectlyjoined with the apertures of said two or more reaction containers,controls said on-mount measuring end transfer mechanism such that saidlight guide portions of said coupling ends and said light guide portionof said measuring end are successively optically connected, andinstructs a measurement by said measuring device.
 2. An automaticresponse/light measurement device according to claim 1, wherein saidmeasuring device has a plurality of types of specific wavelengthmeasuring devices capable of receiving light of specific wavelengths orspecific wavelength bands, each of which has a measuring end having atleast one light guide portion that is optically connected to said lightguide portions of the coupling ends, and a measuring end bundlingportion that bundles in parallel said plurality of measuring ends, andsaid measuring ends are movable in parallel on said mount by means ofsaid on-mount measuring end transfer mechanism, and said measurementcontrol portion, by means of the movement of said measuring ends,controls said on-mount measuring end transfer mechanism such that saidlight guide portions of said coupling ends and said light guide portionsof said measuring ends of said specific wavelength measuring devices aresuccessively optically connected.
 3. An automatic response/lightmeasurement device according to claim 1, wherein said container grouphas sealing lids which have transparency, that are mounted on theapertures of said reaction containers and seal said reaction containers,said sealing lids are joinable with said coupling ends, and saidmeasurement control portion controls said mount transfer mechanism suchthat said mount is moved so that said sealing lids are mounted on saidcoupling ends, and said coupling ends are indirectly joined with theapertures of said reaction containers via said sealing lids.
 4. Anautomatic response/light measurement device according to claim 1,wherein said mount transfer mechanism makes said mount relativelymovable in a vertical direction with respect to said container group,and said measurement control portion, after controlling said mounttransfer mechanism to indirectly join the coupling ends via the sealinglids such that they cover the apertures of said reaction containers,performs control such that it presses or shakes the sealing lidscovering said apertures.
 5. An automatic response/light measurementdevice according to claim 1, having a heating portion that is able toheat said coupling ends.
 6. An automatic response/light measurementdevice according to claim 1, having; a temperature controller thatperforms temperature control of the interior of said reaction containersby having a temperature source provided such that, with respect to saidreaction containers having a lower side wall section and an upper sidewall sections positioned further on the upper side than the lower sidewall section, it is able to make contact with or approach said lowerside wall sections, and a heating portion provided such that it is ableto make contact with or approach said upper side wall sections, and thathas a heat source that is able to heat said upper side wall sections. 7.An automatic response/light measurement device according to claim 1,wherein said measurement mount is provided to a nozzle head having asuction-discharge mechanism that performs suction and discharge ofgases, and one or two or more nozzles that detachably mount dispensingtips in which the suction and the discharge of liquids is possible bymeans of said suction-discharge mechanism, and said mount transfermechanism has a nozzle head transfer mechanism that makes the nozzlehead relatively movable between said container groups.
 8. An automaticresponse/light measurement device according to claim 1, wherein saidcontainer group comprises two or more exclusive regions corresponding tothe nozzles of the respective groups, which comprise one or two or morenozzles, in which nozzles of a single group enter and the nozzles ofother groups do not enter, and the respective exclusive regions at thevery least have at least one reaction container, one or two or moreliquid housing parts that house reaction solutions used in thereactions, and sealing lids that are transportable to said reactioncontainers using said coupling ends and are able to seal said reactionsolutions housed in said reaction containers, and said mount isextendingly provided across all of said exclusive regions such that thecoupling ends of said measurement mount are associated such thatcoupling ends of a single group, which comprises one or two or morecoupling ends, enter said respective exclusive regions and the couplingends of other groups do not enter.
 9. An automatic response/lightmeasurement device comprising: a nozzle head provided with asuction-discharge mechanism that performs suction and discharge ofgases, and one or two or more nozzles that detachably mount dispensingtips in which the suction and the discharge of liquids is possible bymeans of the suction-discharge mechanism; a container group having atthe very least one or two or more liquid housing parts that housereaction solutions used for various reactions, a liquid housing partthat houses a magnetic particle suspension in which magnetic particlesthat are able to capture a target compound are suspended, a liquidhousing part that houses a sample, one or two or more liquid housingparts that house a solution for separating and extracting of the targetcompound, and two or more reaction containers; a nozzle head transfermechanism that makes an interval between said nozzle head and saidcontainer group relatively movable; a magnetic force part that is ableto adsorb said magnetic particles on an inner wall of the dispensingtips mounted on said nozzles; a measurement mount provided to saidnozzle head, and provided with two or more coupling ends that aredirectly or indirectly joinable with apertures of said reactioncontainers, and have light guide portions that optically connect withthe interior of the joined reaction containers; a measuring deviceprovided on the mount, that has measuring ends having light guideportions that optically connect with said light guide portions of saidcoupling ends, and is able to receive light based on an optical statewithin said reaction container via the measuring ends; an on-mountmeasuring end transfer mechanism that makes said measuring ends movableon said mount along the movement path passed by the two or more couplingends; and a magnetic force part that is able to apply or remove amagnetic force that is able to adsorb said magnetic particles on aninner wall of the dispensing tips mounted on said nozzles; and has aseparation and extraction control that, at the very least, controls saidsuction-discharge mechanism, said nozzle head transfer mechanism, andsaid magnetic force part and controls the separation and the extractionof the target compound; and a measurement control portion that, at thevery least, controls said suction-discharge mechanism and said nozzlehead transfer mechanism, and following movement of said mount such thatsaid coupling ends simultaneously directly or indirectly join with theapertures of said two or more reaction containers, controls saidon-mount measuring end transfer mechanism such that said light guideportions of said coupling ends and light guide portions of saidmeasuring ends are successively optically connected, and instructs ameasurement by said measuring device.
 10. An automatic response/lightmeasurement device according to claim 9, wherein said measuring devicehas a plurality of types of specific wavelength devices capable ofreceiving light of specific wavelengths or specific wavelength bands,each of which has a measuring end having at least one light guideportion that is optically connected to said light guide portions of thecoupling ends, and a measuring end bundling portion that bundles theinterval between the plurality of measuring ends in parallel, and saidmeasuring ends are movable in parallel on said mount by means of saidon-mount measuring end transfer mechanism, and said measurement controlportion controls said on-mount measuring end transfer mechanism suchthat, by means of the movement of said measuring ends, said light guideportions of said coupling ends and said light guide portions of themeasuring ends of said specific wavelength measuring devices aresuccessively optically connected.
 11. An automatic response/lightmeasurement device according to claim 9, wherein said container grouphas sealing lids which have transparency and are able to seal thereaction containers by fitting with the apertures of said reactioncontainers, said sealing lids are mountable on said coupling ends, saidmeasuring device is able to receive light based on an optical statewithin said reaction containers via said coupling ends and said sealinglids, and in addition, further has a sealing control part that controlssaid nozzle head transfer mechanism such that said sealing lids aresimultaneously mounted on said coupling ends, and said measurementcontrol portion, following control of said nozzle head transfermechanism such that the coupling ends are simultaneously joined with theapertures of said reaction containers indirectly via said sealing lids,controls said on-mount measuring end transfer mechanism such that saidlight guide portions of said coupling ends and light guide portions ofsaid measuring ends are successively optically connected.
 12. Anautomatic response/light measurement device according to claim 9,further having a mount Z axis transfer mechanism that makes saidmeasurement mount provided to said nozzle head movable in a verticaldirection with respect to the nozzle head, and further having a pressingand the like control part that, following control of the mount Z axistransfer mechanism and indirectly joining the coupling ends with theapertures of said reaction containers, performs control such that thesealing lids covering the apertures are pressed or shaken.
 13. Anautomatic response/light measurement device according claim 9, having aheating portion that is able to heat said coupling ends.
 14. Anautomatic response/light measurement device according to claim 9 having:a temperature controller having a temperature source which is providedsuch that, with respect to said reaction container having a lower sidewall section and an upper side wall section positioned further on theupper side of the lower side wall section, it is able to make contactwith or approach said lower side wall sections, and that performstemperature control of the interior of said reaction containers; and aheating portion which is provided such that it is able to make contactwith or approach said upper side wall sections, and that has a heatsource that is able to heat said upper side wall sections.
 15. Anautomatic response/light measurement device according to claim 9,wherein said container group comprises two or more exclusive regionscorresponding to the nozzles of the respective groups, which compriseone or two or more nozzles, in which nozzles of a single group enter andthe nozzles of other groups do not enter, and the respective exclusiveregions at the very least have at least one reaction container, one ortwo or more liquid housing parts that house reaction solutions used inthe reactions, a liquid housing part that houses a magnetic particlesuspension in which magnetic particles that are able to capture a targetcompound are suspended, a liquid housing part that houses a sample, twoor more liquid housing parts that house a solution for separating andextracting of the target compound, and sealing lids that aretransportable to said reaction containers using said coupling ends andare able to seal said reaction solutions housed in said reactioncontainers, said mount is extendingly provided across all of saidexclusive regions such that the coupling ends of said measurement mountare such that the coupling ends of a single group which comprises one ortwo or more coupling ends, enter each of said respective exclusiveregions, and the coupling ends of other groups do not enter, said nozzlehead transfer mechanism is controlled such that the nozzles of a singlegroup enter said respective exclusive regions and the nozzles of theother groups do not enter, and there is further provided an exclusiveregion control part that controls said on-mount measuring end transfermechanism such that said coupling ends of a single group enter saidrespective exclusive regions and the coupling ends of the other groupsdo not enter.
 16. An automatic response/light measurement method, thatperforms measurement by; moving a measurement mount to which two or morecoupling ends having light guide portions are provided, with respect toapertures of two or more reaction containers arranged in a containergroup, directly or indirectly simultaneously joining the apertures ofsaid reaction containers and said coupling ends, and opticallyconnecting the interior of the joined reaction containers and said lightguide portions provided to the coupling ends, performing temperaturecontrol within the reaction containers, moving the measuring endsprovided to the measuring device on the mount along the movement pathpassed by the two or more coupling ends, so that said light guideportions provided to said coupling ends and light guide portions of saidmeasuring ends are successively optically connected, and making saidmeasuring device receive light based on an optical state within saidreaction containers, via said measuring ends.
 17. An automaticresponse/light measurement method according to claim 16, wherein aplurality of types of specific wavelength measuring devices that areable to receive light of specific wavelengths or specific wavelengthbands at the time of said measurement are provided as said measuringdevice, and light guide portions of measuring ends of the specificwavelength measuring devices are optically connected with said lightguide portions of said coupling ends and are able to receive light ofspecific wavelengths or specific wavelength bands based on an opticalstate within said reaction containers via the measuring ends, andmeasurement is performed by bundling said measuring ends of saidplurality of types of specific wavelength measuring devices and movingthese on said mount in parallel, to thereby successively opticallyconnected said light guide portions provided to said coupling ends andlight guide portions of said measuring ends, and making said specificwavelength measuring devices receive light of specific wavelengths orspecific wavelength bands based on the optical state within saidreaction containers, via said measuring ends.
 18. An automaticresponse/light measurement method according to claim 16, that moves saidmount with respect to two or more sealing lids which have transparency,that are arranged in said container group and are fittable with theapertures of said reaction containers, and moves said mount with respectto the apertures of said reaction containers following simultaneousmounting of the sealing lids on said coupling ends.
 19. An automaticresponse/light measurement method according to claim 16 that, followingmounting of the reaction containers on said measurement mount, performspressing or shaking with respect to the sealing lids covering theapertures of said reaction containers.
 20. An automatic response/lightmeasurement method, that performs measurement by: detachably mountingdispensing tips on nozzles provided to nozzle heads, which performsuction and discharge of gases, separating a target compound using; anozzle head transfer mechanism that relatively moves between a magneticforce part, said nozzle head, and a container group, a magnetic particlesuspension in which magnetic particles that are able to capture thetarget compound housed in the container group are suspended, a sample,and a solution for separating and extracting of the target compound,introducing the separated target compound and a reaction solution usedfor a reaction into a plurality of reaction containers provided to thecontainer group, moving at the very least by means of said nozzle headtransfer mechanism, a measurement mount that, in addition to beingprovided to said nozzle head, is provided with two or more coupling endshaving light guide portions, with respect to apertures of the reactioncontainers, directly or indirectly simultaneously joining the aperturesof said reaction containers and said coupling ends, and opticallyconnecting the interior of the joined reaction containers and the lightguide portions provided to the coupling ends, performing temperaturecontrol within the reaction containers, moving the measuring endsprovided to the measuring device on the mount along the movement pathpassed by the two or more coupling ends, so that the light guideportions of said coupling ends and the light guide portions of saidmeasuring ends are optically successively connected, and making saidmeasuring device receive light based on an optical state within saidreaction containers, via said measuring ends.
 21. An automaticresponse/light measurement method according to claim 20, wherein at thetime of directly or indirectly joining the apertures of said reactioncontainers and said coupling ends, and performing temperature controlwithin the reaction containers, condensation on said coupling ends isdirectly or indirectly prevented by a heat source positioned further onan upper side than a lower side wall section of said reaction containerand provided making contact with or approaching an upper side section ofthe reaction container, according to temperature control of atemperature source provided making contact with or approaching saidlower side wall section.
 22. An automatic response/light measurementdevice comprising: a container group in which two or more reactioncontainers are arranged; a plurality of types of specific wavelengthmeasuring devices provided with measuring ends having light guideportions that are optically connectable with the interior of saidreaction containers, and that are able to receive light of specificwavelengths or specific wavelength bands based on an optical statewithin said reaction containers via the measuring ends; a measuring endbundling portion that bundles the plurality of measuring ends inparallel; a measuring end transfer mechanism that makes the bundledmeasuring ends relatively movable with respect to said container group;and a measurement control portion that, by moving said measuring endsalong a movement path that successively passes apertures of saidreaction containers, controls said measuring end transfer mechanism suchthat light guide portions of said measuring ends and the interior ofsaid reaction containers are successively optically connected, and, withrespect to said specific wavelength measuring devices, instructs ameasurement by receiving light of said specific wavelengths or specificwavelength bands based on an optical state within said reactioncontainers.
 23. An automatic response/light measurement device accordingto claim 22, further comprising a measurement mount provided with two ormore coupling ends that are directly or indirectly joinable with theapertures of said reaction containers, and that have light guideportions that optically connect with the interior of the joined reactioncontainers, wherein the measuring ends of said specific wavelengthmeasuring device are provided on said mount, and in addition, saidmeasuring end transfer mechanism has a mount transfer mechanism thatmakes said mount relatively movable with respect to said containergroup, and an on-mount measuring end transfer mechanism that makes themeasuring ends of said specific wavelength measuring device movable inparallel on said mount.
 24. A reaction container control systemcomprising: a member of light measurement that measures the opticalstate within a reaction container, the reaction container on an apertureof which is mounted by the member of light measurement, a temperaturecontroller that, with respect to the reaction container having a lowerside wall section of the reaction container and an upper side wallsection positioned on an upper side of the lower side wall section, hasa temperature source provided such that it is able to make contact withor approach said lower side wall section, and that performs temperaturecontrol within said reaction container; and a heating portion that isprovided such that it is able to make contact with or approach saidupper side wall section, and that has a heat source that is able to heatsaid upper side wall section, so as to prevent condensation on themember of light measurement.
 25. A reaction container control systemaccording to claim 24, wherein said reaction container comprises awide-mouthed piping part, and a narrow-mouthed piping part that isformed narrower than the wide-mouthed piping part and is provided on alower side of the wide-mouthed piping part and communicated with thewide-mouthed piping part, a member for light measurement is mountable onthe wide-mouthed piping part, liquids are housable in the narrow-mouthedpiping part, and said lower side wall section and said upper side wallsection are provided to said narrow-mouthed piping part.